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排序方式: 共有656条查询结果,搜索用时 15 毫秒
211.
Annette Maier 《Mathematische Annalen》2014,359(3-4):759-784
We consider (Frobenius) difference equations over \((\mathbb {F}\!_q(s,t), \phi _q)\) where \(\phi _q\) fixes \(t\) and acts on \(\mathbb {F}\!_q(s)\) as the Frobenius endomorphism. We prove that every semisimple, simply-connected linear algebraic group \(\mathcal {G}\) defined over \(\mathbb {F}\!_q\) can be realized as a difference Galois group over \((\mathbb {F} \! _{q^i} (s,t),\phi _{q^i})\) for some \(i \in \mathbb {N}\) . The proof uses upper and lower bounds on the Galois group scheme of a Frobenius difference equation that are developed in this paper. The result can be seen as a difference analogue of Nori’s theorem which states that \(\mathcal {G}(\mathbb {F}\!_q)\) occurs as a (finite) Galois group over \(\mathbb {F}\!_q(s)\) . 相似文献
212.
Stereoselective Metal‐Free Synthesis of β‐Amino Thioesters with Tertiary and Quaternary Stereogenic Centers 下载免费PDF全文
Dr. Annette Bahlinger Dr. Sven P. Fritz Prof. Helma Wennemers 《Angewandte Chemie (International ed. in English)》2014,53(33):8779-8783
β‐Amino thioesters are important natural building blocks for the synthesis of numerous bioactive molecules. An organocatalyzed Mannich reaction was developed which provides direct and highly stereoselective access to acyclic β2‐ and β2,3,3‐amino thioesters with adjacent tertiary and quaternary stereocenters. Mechanistic studies showed that the stereochemical course of the reaction can be controlled by the choice of the substrates. The β‐amino thioesters were further functionalized by, for example, stereoselective decarboxylation to access β2,3‐frameworks. In addition, the value of the β‐amino thioesters was shown in coupling‐reagent‐free peptide synthesis. 相似文献
213.
Peptide Modifications Differentially Alter G Protein‐Coupled Receptor Internalization and Signaling Bias 下载免费PDF全文
Veronika Mäde Stefanie Babilon Dr. Navjeet Jolly Lizzy Wanka Dr. Kathrin Bellmann‐Sickert Dr. Luis E. Diaz Gimenez Dr. Karin Mörl Prof. Dr. Helen M. Cox Prof. Dr. Vsevolod V. Gurevich Prof. Dr. Annette G. Beck‐Sickinger 《Angewandte Chemie (International ed. in English)》2014,53(38):10067-10071
Although G protein‐coupled receptors (GPCRs) are targeted by more clinically used drugs than any other type of protein, their ligand development is particularly challenging. Humans have four neuropeptide Y receptors: hY1R and hY5R are orexigenic, while hY2R and hY4R are anorexigenic, and represent important anti‐obesity drug targets. We show for the first time that PEGylation and lipidation, chemical modifications that prolong the plasma half‐lives of peptides, confer additional benefits. Both modifications enhance pancreatic polypeptide preference for hY2R/hY4R over hY1R/hY5R. Lipidation biases the ligand towards arrestin recruitment and internalization, whereas PEGylation confers the opposite bias. These effects were independent of the cell system and modified residue. We thus provide novel insights into the mode of action of peptide modifications and open innovative venues for generating peptide agonists with extended therapeutic potential. 相似文献
214.
Annette J. Theron Ronald Anderson Morris Madzime Theresa M. Rossouw Helen C. Steel Pieter W. A. Meyer Moloko C. Cholo Luyanda L. I. Kwofie Charles Feldman Gregory R. Tintinger 《Molecules (Basel, Switzerland)》2022,27(24)
There is increasing awareness of an association between the uptake of the HIV integrase inhibitor, dolutegravir, in first-line antiretroviral regimens with unusual weight gain and development of the metabolic syndrome, particularly in African women. Although seemingly unexplored, the development of systemic inflammation linked to the putative pro-inflammatory activity of dolutegravir represents a plausible pathophysiological mechanism of this unusual weight gain. This possibility was explored in the current study undertaken to investigate the effects of dolutegravir (2.5–20 μg/mL) on several pro-inflammatory activities of neutrophils isolated from the blood of healthy, adult humans. These activities included the generation of reactive oxygen species (ROS), degranulation (elastase release) and alterations in the concentrations of cytosolic Ca2+ using chemiluminescence, spectrophotometric and fluorimetric procedures, respectively. Exposure of neutrophils to dolutegravir alone resulted in the abrupt, dose-related, and significant (p < 0.0039–p < 0.0022) generation of ROS that was attenuated by the inclusion of the Ca2+-chelating agent, EGTA, or inhibitors of NADPH oxidase (diphenyleneiodonium chloride, DPI), phospholipase C (U733122), myeloperoxidase (sodium azide) and phosphoinositol-3-kinase (wortmannin). In addition, exposure to dolutegravir augmented the release of elastase by stimulus-activated neutrophils. These pro-inflammatory effects of dolutegravir on neutrophils were associated with significant, rapid, and sustained increases in the concentrations of cytosolic Ca2+ that appeared to originate from the extracellular compartment, seemingly consistent with an ionophore-like property of dolutegravir. These findings are preliminary and necessitate verification in the clinical setting of HIV infection. Nevertheless, given the complex link between inflammation and obesity, these pro-inflammatory interactions of dolutegravir with neutrophils may contribute to unexplained weight gain, possibly via the development of insulin resistance. 相似文献
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219.
Annette Thierry Cyril Mathieu Christine Straup Jean‐Claude Wittmann Bernard Lotz Victor Da Costa Jacques Le Moigne 《Macromolecular Symposia》2001,166(1):43-58
Control of structural order at the molecular level for both conventional linear polymers and conjugated polymers with valuable opto‐electronic properties has major consequence on the macroscopic properties of these polymers. Though the traditional means of orientation of polymer was mechanical deformation, presently extensive works are concerned with a more controlled way of orientation: epitaxial crystallisation. Most of the first documented examples of epitaxial growth of conventional polymers on single crystals followed the well‐established geometrical rules of best matching. However, recent examples show off more subtle rules of selection. Analogous cases, following or breaking the matching rules, have been observed for diacetylenes ordered via epipolymerisation on single crystals. Hereafter, representative examples of the structural matching rules are depicted first, and then recent examples, which depart from the simple geometrical fitting, are described. The analysis of the former leads to define the subtle matching rules applying for polymers linked to their conformational adaptability. The analysis of the latter gives the opportunity to discuss the relative influence of geometrical and molecular interactions between the deposit and the substrate. 相似文献
220.