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排序方式: 共有403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 Gaponik Yury P. Rakovich Matthias Gerlach John F. Donegan Diana Savateeva Andrey L. Rogach 《Nanoscale research letters》2006,1(1):68-73
We have studied the photoluminescence and Raman spectra of a system consisting of a polystyrene latex microsphere coated by CdTe colloidal quantum dots. The cavity-induced enhancement of the Raman scattering allows the observation of Raman spectra from only a monolayer of CdTe quantum dots. Periodic structure with very narrow peaks in the photoluminescence spectra of a single microsphere was detected both in the Stokes and anti-Stokes spectral regions, arising from the coupling between the emission of quantum dots and spherical cavity modes. 相似文献
4.
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
5.
Broadband Light Absorption and Efficient Charge Separation Using a Light Scattering Layer with Mixed Cavities for High‐Performance Perovskite Photovoltaic Cells with Stability
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Byeong Cheul Moon Jung Hyo Park Dong Ki Lee Nikolai Tsvetkov Ilwoo Ock Kyung Min Choi Jeung Ku Kang 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(30)
CH3NH3PbI3 is one of the promising light sensitizers for perovskite photovoltaic cells, but a thick layer is required to enhance light absorption in the long‐wavelength regime ranging from PbI2 absorption edge (500 nm) to its optical band‐gap edge (780 nm) in visible light. Meanwhile, the thick perovskite layer suppresses visible‐light absorption in the short wavelengths below 500 nm and charge extraction capability of electron–hole pairs produced upon light absorption. Herein, we find that a new light scattering layer with the mixed cavities of sizes in 100 and 200 nm between transparent fluorine‐doped tin oxide and mesoporous titanium dioxide electron transport layer enables full absorption of short‐wavelength photons (λ < 500 nm) to the perovskite along with enhanced absorption of long‐wavelength photons (500 nm < λ < 780 nm). Moreover, the light‐driven electric field is proven to allow efficient charge extraction upon light absorption, thereby leading to the increased photocurrent density as well as the fill factor prompted by the slow recombination rate. Additionally, the photocurrent density of the cell with a light scattering layer of mixed cavities is stabilized due to suppressed charge accumulation. Consequently, this work provides a new route to realize broadband light harvesting of visible light for high‐performance perovskite photovoltaic cells. 相似文献
6.
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
7.
Molecular models of all known subtypes (A1, A2A, A2B, and A3) of the human adenosine receptors were built in homology with bovine rhodopsin. These models include the transmembrane domain as well as all extracellular and intracellular hydrophilic loops and terminal domains. The molecular docking of adenosine and 46 selected derivatives was performed for each receptor subtype. A binding mode common for all studied agonists was proposed, and possible explanations for differences in the ligand activities were suggested. 相似文献
8.
9.
Ewa Szczurowska Eszter Sznti-Pintr Nikolai Chetverikov Alena Randkov Eva Kudov Jan Jakubík 《International journal of molecular sciences》2023,24(1)
Muscarinic acetylcholine receptors expressed in the central nervous system mediate various functions, including cognition, memory, or reward. Therefore, muscarinic receptors represent potential pharmacological targets for various diseases and conditions, such as Alzheimer’s disease, schizophrenia, addiction, epilepsy, or depression. Muscarinic receptors are allosterically modulated by neurosteroids and steroid hormones at physiologically relevant concentrations. In this review, we focus on the modulation of muscarinic receptors by neurosteroids and steroid hormones in the context of diseases and disorders of the central nervous system. Further, we propose the potential use of neuroactive steroids in the development of pharmacotherapeutics for these diseases and conditions. 相似文献
10.
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