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排序方式: 共有492条查询结果,搜索用时 15 毫秒
1.
Robert G Clyde James L Bown Ted R Hupp Nikolai Zhelev John W Crawford 《Journal of the Royal Society Interface》2006,3(10):617-627
The cell cycle is implicated in diseases that are the leading cause of mortality and morbidity in the developed world. Until recently, the search for drug targets has focused on relatively small parts of the regulatory network under the assumption that key events can be controlled by targeting single pathways. This is valid provided the impact of couplings to the wider scale context of the network can be ignored. The resulting depth of study has revealed many new insights; however, these have been won at the expense of breadth and a proper understanding of the consequences of links between the different parts of the network. Since it is now becoming clear that these early assumptions may not hold and successful treatments are likely to employ drugs that simultaneously target a number of different sites in the regulatory network, it is timely to redress this imbalance. However, the substantial increase in complexity presents new challenges and necessitates parallel theoretical and experimental approaches. We review the current status of theoretical models for the cell cycle in light of these new challenges. Many of the existing approaches are not sufficiently comprehensive to simultaneously incorporate the required extent of couplings. Where more appropriate levels of complexity are incorporated, the models are difficult to link directly to currently available data. Further progress requires a better integration of experiment and theory. New kinds of data are required that are quantitative, have a higher temporal resolution and that allow simultaneous quantitative comparison of the concentration of larger numbers of different proteins. More comprehensive models are required and must accommodate not only substantial uncertainties in the structure and kinetic parameters of the networks, but also high levels of ignorance. The most recent results relating network complexity to robustness of the dynamics provide clues that suggest progress is possible. 相似文献
2.
Elisabeth M. Haberl Thomas S. Weiss Georg Peschel Kilian Weigand Nikolai Khler Josch K. Pauling Jürgen J. Wenzel Marcus Hring Sabrina Krautbauer Gerhard Liebisch Christa Buechler 《International journal of molecular sciences》2021,22(10)
Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology. 相似文献
3.
Nikolai N. Kukharkin 《Journal of scientific computing》1995,10(4):409-448
General conditions for the formation of long-lived coherent vortices in decaying and force-driven 2-D turbulence are investigated. It is shown by a series of numerical simulations that the emergence of closed streamlines leading to the trapped trajectories of vorticity is a necessary, but not sufficient condition for this phenomenon, so that these trapped trajectories may be considered only as seed vortices. Numerical experiments which demonstrate the relations between phase correlations, finite-size effects, and the formation of coherent vortices in 2-D decaying turbulence are presented. It is shown that there is a universal dimensionless time for the onset of intermittency in the flow which corresponds to the time of establishment of phase correlations. The stricter conditions for appearance of coherent vortices in forced turbulence in comparison with decaying turbulence are associated with phase mixing introduced by random forcing. The universal features of decaying turbulence are discussed in terms of phase portraits based on inviscid constants of motion and their decay rates. 相似文献
4.
Igor Solodov Markus Rahammer Nikolai Gulnizkij Marc Kreutzbruck 《Journal of Nondestructive Evaluation》2016,35(3):48
A selective acoustic activation of defects based on the concept of local defect resonance enables to enhance considerably the intensity of defect vibrations and makes it possible to reduce the input acoustic powers to the levels permissible for noncontact nondestructive inspection. Since for cm-size defects in composite materials, the LDR frequencies lie in the low kHz-range, the resonant noncontact activation shifts to an audible frequency range and can be provided by conventional sonic equipment. In this paper, the feasibility of the resonant noncontact inspection is validated for the most “problematic” methodologies of nonlinear, thermosonic and shearosonic NDE that usually require an elevated acoustic power and, therefore, a reliable contact between the specimen and the transducer. In contrast, the noncontact versions developed employ commercial loudspeakers which can simultaneously insonify large areas and be applied for a contactless sonic inspection of different materials and various scale components. 相似文献
5.
6.
Albena Momchilova Roumen Pankov Alexander Alexandrov Tania Markovska Stefan Pankov Plamen Krastev Galya Staneva Evgenia Vassileva Nikolai Krastev Adriana Pinkas 《International journal of molecular sciences》2022,23(14)
Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products—ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine. 相似文献
7.
Vadim E. Filatov Dmitrii A. Iuzabchuk Viktor A. Tafeenko Yuri K. Grishin Vitaly A. Roznyatovsky Dmitrii A. Lukianov Yulia A. Fedotova Maxim A. Sukonnikov Dmitry A. Skvortsov Nikolai V. Zyk Elena K. Beloglazkina 《International journal of molecular sciences》2022,23(12)
In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD. 相似文献
8.
Chloride and Indium‐Chloride‐Complex Inorganic Ligands for Efficient Stabilization of Nanocrystals in Solution and Doping of Nanocrystal Solids 下载免费PDF全文
Vladimir Sayevich Chris Guhrenz Maria Sin Volodymyr M. Dzhagan Alexander Weiz Daniel Kasemann Eike Brunner Michael Ruck Dietrich R. T. Zahn Karl Leo Nikolai Gaponik Alexander Eychmüller 《Advanced functional materials》2016,26(13):2163-2175
Here, the surface functionalization of CdSe and CdSe/CdS core/shell nanocrystals (NCs) with compact chloride and indium‐chloride‐complex ligands is reported. The ligands provide not only short interparticle distances but additionally control doping and passivation of surface trap states, leading to enhanced electronic coupling in NC‐based arrays. The solids based on these NCs show an excellent electronic transport behavior after heat treatment at the relatively low temperature of 190 °C. Indeed, the indium‐chlorido‐capped 4.5 nm CdSe NC based thin‐film field‐effect transistor reaches a saturation mobility of μ = 4.1 cm2 (V s)?1 accompanied by a low hysteresis, while retaining the typical features of strongly quantum confined semiconductor NCs. The capping with chloride ions preserves the high photoluminescence quantum yield ( ≈ 66%) of CdSe/CdS core/shell NCs even when the CdS shell is relatively thin (six monolayers). The simplicity of the chemical incorporation of chlorine and indium species via solution ligand exchange, the efficient electronic passivation of the NC surface, as well as their high stability as dispersions make these materials especially attractive for wide‐area solution‐processable fabrication of NC‐based devices. 相似文献
9.
10.
Jie Liu Volker Ventzke Peter Staron Norbert Schell Nikolai Kashaev Norbert Huber 《Metallurgical and Materials Transactions A》2014,45(1):16-28
Post-weld heat treatment is carried out on the laser beam welded γ-TiAl-based alloy Ti-48Al-1Cr-1.5Nb-1Mn-0.2Si-0.5B (at. pct). The macro/microstructure and mechanical properties of both as-welded and heat-treated specimens are investigated by radiography, SEM, and tensile tests. Moreover, high energy synchrotron X-ray diffraction is performed to measure the residual stresses and evaluate the microstructure evolution. It is found that the residual stresses are distributed in a three-peak shape in the region of the weld zone and heat-affected zone of the as-welded specimen due to the microstructural transformation and heat softening. The residual stresses are largely relieved after the heat treatment. The heat-treated specimens have a near fully lamellar microstructure and show balanced mechanical properties of strength and ductility. The diffraction shows that the phase transformation from α 2 to γ takes place under tensile load at 1023 K (750 °C), and the grain size and lamellar spacing are refined in the weld zone. Finally, the fracture mechanisms are found to be controlled by the local stress concentration-induced strain misfit between α 2 and γ phases in the near γ grains and delamination and debonding in the lamellae. Boride ribbons of 5 μm in the near fully lamellar microstructure are found not to be detrimental to the tensile properties. 相似文献