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排序方式: 共有409条查询结果,搜索用时 0 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.
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
7.
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
8.
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
9.
Statistical testing for sufficient control chart performances during monitoring of grouped processes
Kevin Nikolai Kostyszyn Tobias Claus Brandstätter Thomas Vollmer Robert Schmitt 《Quality and Reliability Engineering International》2021,37(6):2555-2567
With ISO 7870-8, a standardized application of charting techniques for short runs and small mixed batches was presented in 2017. Similar to various scientific approaches, it requires that sample values from grouped processes follow nearly identical distributions. In practice, however, there tend to be differences between distribution parameters. Moreover, equal parameters do not ensure that distributions are properly aligned to the center line and control limits of the chart. These facts can lead to undesired control chart performances which can be expressed by average run lengths (ARL) during in-control and out-of-control conditions. In this work, a statistical test for sufficient control chart performances during monitoring of grouped processes based on preliminary samples is proposed. Control chart performances are defined as sufficient when they deviate within acceptable ranges from usual performances during single process monitoring in mass production. The ARL resulting from estimated distributions and planned production sequences is used as test statistic and calculated via the Markov chain approach. Exemplary tests are executed for scenarios with individuals and cumulated sum (CUSUM) charts. A simulative determination of error rates resulting from the ARL-based testing demonstrates its effectiveness in testing for sufficient control chart performances compared to an indirect testing with Levene's test and a one-way analysis of variance (ANOVA). 相似文献
10.
Development of Saturable Absorbers for Laser Passive Q‐Switching near 1.5 μm Based on Transparent Ceramic Co2+:MgAl2O4 下载免费PDF全文
Adrian Goldstein Pavel Loiko Zeev Burshtein Nikolai Skoptsov Ilya Glazunov Ehud Galun Nikolai Kuleshov Konstantin Yumashev 《Journal of the American Ceramic Society》2016,99(4):1324-1331
We describe the development of a reasonable cost Co2+:MgAl2O4 transparent ceramic plates fabrication technology that allows the producing of parts functioning as passive laser Q‐switches in the 1.3–1.7 μm domain. The main relevant material characteristics were measured. The absorption band, positioned between 1.2 and 1.7 μm, is typical of the 4A2 (4F) → 4T1 (4F) transition of Co2+ substituting Mg2+ ions in their Td symmetry sites. The measured ground‐state absorption cross section σgs = 2.9 × 10?19 cm2, saturation contrast γ = 0.12, and depleted ground‐state recovery time τ2 = 110–430 ns render such parts suitable for the intended application. The radiative lifetime was estimated as . The spin‐orbit splitting constant was estimated as ξSL??150 cm?1 for the 4F parent ground state, and ξSL ? –575 cm?1 for the 4P parent excited state. Obtained specimens had a transmission of ~80% (t = 2 mm, λ = 600 nm) and included some opaque, white spots. Further improvement of host optical transmission and resistance to laser damage are necessary. 相似文献