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81.
Ohne ZusammenfassungMit 6 Textabbildungen.  相似文献   
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Recent advances in virology, gene therapy, and molecular and cell biology have provided insight into the mechanisms through which viruses can boost the anti-tumor immune response, or can infect and directly kill tumor cells. A recent experimental report (Bridle et al. in Molec. Ther. 18(8):1430–1439, 2010) showed that a sequential treatment approach that involves two viruses that carry the same tumor antigen leads to an improved anti-tumor response compared to the effect of each virus alone. In this article, we derive a mathematical model to investigate the anti-tumor effect of two viruses, and their interactions with the immune cells. We discuss the conditions necessary for permanent tumor elimination and, in this context, we stress the importance of investigating the long-term effect of non-linear interactions. In particular, we discuss multi-stability and multi-instability, two complex phenomena that can cause abrupt transitions between different states in biological and physical systems. In the context of cancer immunotherapies, the transitions between a tumor-free and a tumor-present state have so far been associated with the multi-stability phenomenon. Here, we show that multi-instability can also cause the system to switch from one state to the other. In addition, we show that the multi-stability is driven by the immune response, while the multi-instability is driven by the presence of the virus.  相似文献   
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Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases.  相似文献   
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We investigated the class II B genes in free-ranging population of the ring-necked pheasant Phasianus colchicus by a combination of restriction fragment length polymorphism (RFLP), polymerase chain reaction (PCR), and DNA sequencing. Special attention was paid to the variation in the second exon, which encodes the peptide-binding 1-domain. The population was introduced, but it still exhibited major histocompatibility complex polymorphism with at least three segregating class II B haplotypes and consequently six genotypes. We found two class II B genes associated with each haplotype. The class II B genes of birds had until then only been molecularly characterized in the domestic chicken. the pheasant genes were highly variable, although one of the amplified sequences was found in two different haplotypes. Taken together, the most polymorphic positions (residues 37 and 38) were not identical in any of the predicted protein sequences, but all except one of the motifs had already been foud in the domestic chicken. Structurally important features in mammalian class II B genes were generally conserved also in the pheasant sequences, but the loss of a potential salt bridge constituent (Arg72) in several sequences may suggest a slightly different structure of the adjacent parts of the peptide-binding groove. The pheasant genes are most closely related to the so called B-LBII family in the chicken, indicating that this represents a major line of development among avian class II B genes.The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the accession numbers X75403-X75407. Correspondence to: H. Wittzell, Department of Theoretical Ecology, Ecology Building, Lund University, S-223 62 Lund, Sweden.  相似文献   
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