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11.
Dr. Sabine Lennarz MSc Therese Christine Alich Dr. Tony Kelly Dr. Michael Blind Prof. Dr. Heinz Beck Prof. Dr. Günter Mayer 《Angewandte Chemie (International ed. in English)》2015,54(18):5369-5373
Cellular behavior is orchestrated by the complex interactions of a myriad of intracellular signal transduction pathways. To understand and investigate the role of individual components in such signaling networks, the availability of specific inhibitors is of paramount importance. We report the generation and validation of a novel variant of an RNA aptamer that selectively inhibits the mitogen‐activated kinase pathway in neurons. We demonstrate that the aptamer retains function under intracellular conditions and that application of the aptamer through the patch‐clamp pipette efficiently inhibits mitogen‐activated kinase‐dependent synaptic plasticity. This approach introduces synthetic aptamers as generic tools, readily applicable to inhibit different components of intraneuronal signaling networks with utmost specificity. 相似文献
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Bhurruth-Alcor Y Røst T Jorgensen MR Kontogiorgis C Skorve J Cooper RG Sheridan JM Hamilton WD Heal JR Berge RK Miller AD 《Organic & biomolecular chemistry》2011,9(4):1169-1188
Peroxisome proliferator activated receptors (PPARs) have been shown to have critical roles in fatty acid oxidation, triglyceride synthesis, and lipid metabolism - making them an important target in drug discovery. Here we describe the in silico design, synthesis and in vitro characterisation of a novel series of 2,5-disubstituted indoles as PPARα/γ dual agonists. PPAR activation assays are performed with known agonists diazabenzene (WY14.643), aminopyridine (BRL49653) and bisaryl (L165.041), as positive controls. All the indole compounds synthesized are found to be active PPARα and PPARγ agonists, with particular efficacy from those with 2-naphthylmethyl substitution. This is a useful demonstration of a new de novo design methodology implemented by the protobuild program and its ability to rapidly produce novel modulators for a well characterized drug target. 相似文献
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In 1984, J. X. Lu proved the following statement. Given any k and λ, there exists a constant c(k, λ) such that an RB[v,k,λ] exists for all v > c(k,λ) satisfying the usual necessary conditions. Lu's paper was written in Chinese and, unfortunately, its accessibility is limited. We have translated Lu's paper into English and have also given a new interpretation of his constructions for resolvable block designs. © 1995 John Wiley & Sons, Inc. 相似文献
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Although native chemical ligation (NCL) is emerging as a powerful method for the assembly of (glyco)peptide building blocks, its applicability is reduced when peptide segments are poorly soluble in aqueous buffer. We have found that incorporating reactants in liposomes allows NCL of lipophilic peptides and lipopeptides. Furthermore, the reaction rates of liposome-mediated NCL are higher than traditional reaction conditions resulting in improved yields. [reaction: see text] 相似文献
18.
Therese L Ghalem Z Guillot P Belenguer P 《Analytical and bioanalytical chemistry》2006,386(1):163-168
In radiofrequency glow discharge emission spectrometry (RF-GDOES), the excitation voltage used to create the plasma is applied
to the back or front end of the sample to be analyzed. In this paper we focus on back-applied voltage systems (a configuration
that represents about half of the instruments available on the market), and on applied voltage problems (the power coupling
efficiency and materials analysis are beyond the scope of this study). In the RF-GDOES of nonconductive samples, a voltage
drop develops inside the material. The voltage transfer coefficient is defined as the ratio between the peak voltage in front
of the sample (facing the plasma) and the peak voltage applied to the back of the sample. In this work, we show that it is
possible to increase the voltage transfer coefficient by increasing the capacitance of the sample. The capacitance of a given
nonconductive material depends on its surface, its thickness and its permittivity. Increasing the voltage transfer coefficient
permits higher power deposition in the plasma. This study is based on an electrical equivalent circuit for the discharge device,
which takes into account the sample and reactor capacitances as well as the voltage probes used for the measurements. This
circuit, when modeled by a commercial electrical circuit simulator, gives the voltage transfer coefficient as a function of
the sample capacitance. Different approaches to increasing the sample capacitance and their influence on the voltage transfer
coefficient are presented and related to the 750.4 nm argon line intensity, which is correlated to the electron density. 相似文献
19.
Therese Biedl Angèle M. Hamel Alejandro López-Ortiz 《Discrete Applied Mathematics》2010,158(15):1579-1586
We consider the problem of sorting a permutation using a network of data structures as introduced by Knuth and Tarjan. In general the model as considered previously was restricted to networks that are directed acyclic graphs (DAGs) of stacks and/or queues. In this paper we study the question of which are the smallest general graphs that can sort an arbitrary permutation and what is their efficiency. We show that certain two-node graphs can sort in time Θ(n2) and no simpler graph can sort all permutations. We then show that certain three-node graphs sort in time Ω(n3/2), and that there exist graphs of k nodes which can sort in time Θ(nlogkn), which is optimal. 相似文献
20.
Halogenated analogues of ethyl diazoacetate are synthesised by a novel and highly efficient procedure and give halocyclopropanes in good to excellent yields when exposed to a Rh(ii) catalyst in the presence of alkenes. 相似文献