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Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.  相似文献   
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Recent studies on cyclin-dependent kinase (CDK) inhibitors have revealed that small molecule drugs have become very attractive for the treatment of cancer and neurodegenerative disorders. Most CDK inhibitors have been developed to target the ATP binding pocket. However, CDK kinases possess a very similar catalytic domain and three-dimensional structure. These features make it difficult to achieve required selectivity. Therefore, inhibitors which bind outside the ATP binding site present a great interest in the biomedical field, both from the fundamental point of view and for the wide range of their potential applications. This review tries to explain whether the ATP competitive inhibitors are still an option for future research, and highlights alternative approaches to discover more selective and potent small molecule inhibitors.  相似文献   
4.
Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by favoring the centralization of hydrophobic residues with the simultaneous exposure to polar residues. The degree of compatibility of the residue distribution, with the model of the concentration of hydrophobic residues in the center of the molecule, with the simultaneous exposure of polar residues is determined by the sequence of amino acids in the chain. The fuzzy oil drop model enables the quantification of the degree of compatibility of the hydrophobicity distribution observed in the protein to a form fully consistent with the Gaussian 3D function, which expresses an idealized distribution that meets the preferences of the polar water environment. The varied degrees of compatibility of the distribution observed with the idealized one allow the prediction of preferences to interactions with molecules of different polarity, including water molecules in particular. This paper analyzes a set of proteins with different levels of hydrophobicity distribution in the context of the solubility of a given protein and the possibility of complex formation.  相似文献   
5.
An image watermarking technique based on the concept of JPEG2000 algorithm is proposed. Biorthogonal wavelet 9/7 transform is used to provide a set of coefficients suitable for watermark embedding. The statistical properties of different subbands are analyzed in order to choose the number of decomposition levels and position of subbands, which will assure the best compromise between the watermark transparency and robustness. The JPEG2000 quantization is applied to avoid insignificant wavelet coefficients, while the remaining ones are used for watermarking. The optimal and blind watermark detection is based on the nonlinear score function and appropriate model of coefficients distribution. The performance of the proposed procedure is tested on examples with various images, showing robustness under different attacks, while maintaining high image quality.  相似文献   
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This study examines the effect of pitch concentration, rate of heating, soak temperature and time of soak upon the optical texture of cokes prepared from the co-carbonizations of a coal (Oxcroft-Clowne, NCB Rank 802) and three vitrains of NCB Rank 204, 801, 902 with Ashland A240 petroleum pitch. Using the coal (Rank 802) with 10 wt % and 25 wt % additions of pitch caused progressive penetration of the pitch into the coal with a resultant development of a mozaic anisotropy in the coke to replace partially the original coke isotropy. With 50 wt % addition of pitch almost all of the coal particles, 600 to 1100 μm in size, were modified during carbonization. Some pitch coke was formed. For the coal and three vitrains with increasing rates of co-carbonization from 0.5–10 K min?1 to 1200 K, using 25 wt % of A240 pitch, resultant cokes showed progressively increased extents of modification. For the two vitrains (Rank 801, 902) soaking at temperatures of 650–690 K caused a decrease in the extent of modification of isotropic coke when compared with the coke of HTT 1200 K. Evidently fast heating rates create the conditions of fluidity necessary for the pitch to modify the coal leading to growth of mesophase and anisotropic coke.  相似文献   
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In this paper the process of silicon anisotropic etching in KOH solutions containing isopropyl alcohol in a wide concentration range is extensively studied. Though the alcohol does not take part in the etching process itself, it strongly affects the etching results. Both etch rates and the roughness of etched surfaces depend on the alcohol concentration in the etching solution, which is connected with the adsorption phenomena on the etched surface. The surface coverage with alcohol depends on the level of saturation of the etching solution and crystallographic orientation of an etched surface. It was observed that the best morphology of (1 1 0) surface was achieved just below saturation level with IPA whereas the (1 0 0) surfaces were improving above the saturation. A model, which explains these phenomena, was proposed. Based on this model, a simple way of selection of the composition of KOH solutions with alcohol additives, assuring optimization of etching results was suggested. The method is restricted to surface tension measurements and allows one to avoid elaborated etching experiments.  相似文献   
9.
Abstract: The concept of linked oscillators in biological control systems has long been established. Frequency entrainment is a predominant explanation behind many biological rhythms. In this paper a preliminary examination of electroencephalographic entrainment is made to survey the possibility and methods of achieving signal entrainment at the highest level of neurological organization and function. A model of the thalamocortical system is employed to generate simulated electroencephalographic signals and is tested in various configurations in the search for entrainment under very simple conditions. Additionally, an analysis of the coupled Van der Pol model of the circadian rhythm controller is performed to identify the possibility of affecting that system with a drastically different coupling input signal. We were able to conclude that overall signal shape can have a significant impact on the entrainment characteristics of the system. Due to the nature of the underlying mathematical structure of the model, by examining the circadian rhythm controller, we found that it is unsuitable for entrainment to an incident entraining signal of much higher frequency.  相似文献   
10.
The authors tested whether adherence to simultaneous health behavior changes was unitary or domain specific among 76 women who modified smoking, eating, and physical activity to accomplish smoking cessation plus weight control. Random-effects regression analyses showed that adherence to both smoking and diet plans declined linearly and covaried positively; their association tended to grow stronger over time. In contrast, physical activity plan adherence did not change over time and was unrelated to other domains. At the end of treatment, 65%, 30.5%, and 25% adhered well or excellently to smoking, diet, and activity treatments, respectively. Findings support both unitary and domain-specific aspects of adherence and suggest that among smokers, smoking and eating behaviors may have similarities unshared by physical activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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