基于多活性代理的分布式入侵检测系统构建分析研究

针对应用了移动代理技术的分布式入侵检测系统在代理安全性和稳定性方面所存在的问题,本文在基于多活性代理复杂信息系统研究方法的指导下,提出了一种新的分布式入侵检测系统结构,即基于多活性代理的分布式入侵检测系统(DIDS-MLA).该系统将传统分布式入侵检测系统的两层结构扩展为三层结构,通过增加的一层结构对系统中各个检测代理活性状态值进行监测,使系统能够在多活性代理协商协调机理的指导下,根据代理活性状态值的变化来调整各代理的工作,从而达到保护系统中代理安全性以及维护系统检测稳定性的目的.在之前的研究工作中,我们仅仅对活性代理进行了定性分析,本文中则进一步提出了一种在分布式入侵检测环境下定量分析代理活性的方法,并在此基础上给出了系统中活性代理的实现思路.最后通过对系统工作流程以及对分布式拒绝服务攻击的检测效果进行分析之后,我们可以看出,本文所设计的DIDS-MLA系统在安全性和稳定性方面比传统分布式入侵检测系统(DIDS)以及基于移动代理的DIDS系统有明显改善,能够在强对抗环境下保证系统检测工作的正常运行.     

CD24 interacts with and promotes the activity of c-src within lipid rafts in breast cancer cells, thereby increasing integrin-dependent adhesion

Expression of the glycosylphosphatidylinositol-anchored membrane protein CD24 correlates with a poor prognosis for many human cancers, and in experimental tumors can promote metastasis. However, the mechanism by which CD24 contributes to tumor progression remains unclear. Here we report that in MTLy breast cancer cells CD24 interacts with and augments the kinase activity of c-src, a protein strongly implicated in promoting invasion and metastasis. This occurs within and is dependent upon intact lipid rafts. CD24-augmented c-src kinase activity increased formation of focal adhesion complexes, accelerated phosphorylation of FAK and paxillin and consequently enhanced integrin-mediated adhesion. Loss and gain of function approaches showed that c-src activity is necessary and sufficient to mediate the effects of CD24 on integrin-dependent adhesion and cell spreading, as well as on invasion. Together these results indicate that c-src is a CD24-activated mediator that promotes integrin-mediated adhesion and invasion, and suggest a mechanism by which CD24 might contribute to tumor progression through stimulating the activity of c-src or another member of the Src family.     

Familial hemophagocytic lymphohistiocytosis: a model for understanding the human machinery of cellular cytotoxicity

Cytotoxic T lymphocytes, natural killer cells, and NKT cells are effector cells able to kill infected cells. In some inherited human disorders, a defect in selected proteins involved in the cellular cytotoxicity mechanism results in specific clinical syndromes, grouped under the name of familial hemophagocytic lymphohistiocytosis. Recent advances in genetic studies of these patients has allowed the identification of different genetic subsets. Additional genetic immune deficiencies may also induce a similar clinical picture. International cooperation and prospective trials resulted in refining the diagnostic and therapeutic approach to these rare diseases with improved outcome but also with improved knowledge of the mechanisms underlying granule-mediated cellular cytotoxicity in humans.     

Dominant missense mutations in ABCC9 cause Cantú syndrome

Cantú syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantú syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantú syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome.     

Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype

The chromosome 17q21.31 deletion syndrome is a genomic disorder characterized by highly distinctive facial features, moderate-to-severe intellectual disability, hypotonia and friendly behavior. Here, we show that de novo loss-of-function mutations in KANSL1 (also called KIAA1267) cause a full del(17q21.31) phenotype in two unrelated individuals that lack deletion at 17q21.31. These findings indicate that 17q21.31 deletion syndrome is a monogenic disorder caused by haploinsufficiency of KANSL1.     

Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm

Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies.