Active probing based Internet service fault management in uncertain and noisy environment

In Internet service fault management based on active probing, uncertainty and noises will affect service fault management. In order to reduce the impact, challenges of Internet service fault management are analyzed in this paper. Bipartite Bayesian network is chosen to model the dependency relationship between faults and probes, binary symmetric channel is chosen to model noises, and a service fault management approach using active probing is proposed for such an environment. This approach is composed of two phases： fault detection and fault diagnosis. In first phase, we propose a greedy approximation probe selection algorithm （GAPSA）, which selects a minimal set of probes while remaining a high probability of fault detection. In second phase, we propose a fault diagnosis probe selection algorithm （FDPSA）, which selects probes to obtain more system information based on the symptoms observed in previous phase. To deal with dynamic fault set caused by fault recovery mechanism, we propose a hypothesis inference algorithm based on fault persistent time statistic （FPTS）. Simulation results prove the validity and efficiency of our approach.

基于贝叶斯模型的高效主动探测算法(英文)

Fault diagnosis on large-scale and complex networks is a challenging task, as it requires efficient and accurate inference from huge data volumes. Active probing is a cost-efficient tool for fault diagnosis. However almost all existing probing-based techniques face the following problems: 1) performing inaccurately in noisy networks; 2) generating additional traffic to the network; 3) high cost computation. To address these problems, we propose an efficient probe selection algorithm for fault diagnosis based on Bayesian network. Moreover, two approaches which could significantly reduce the computational complexity of the probe selection process are provided. Finally, we implement the new proposed algorithm and a former representative probing-based algorithm (BPEA algorithm) on different settings of networks. The results show that, the new algorithm performs much faster than BPEA does without sacrificing the diagnostic quality, especially in large, noisy and multiple-fault networks.

Membrane dual-targeting probes:A promising strategy for fluorescence-guided prostate cancer surgery and lymph node metastases detection

Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

Simultaneous capture of ISG15 conjugating and deconjugating enzymes using a semi-synthetic ISG15-Dha probe

ISG15 is a ubiquitin-like(Ubl) protein attached to substrate proteins by ISG15 conjugating enzymes whose dysregulation is implicated in a multitude of disease processes, but the probing of these enzymes remains to be accomplished. Here, we describe the development of a new activity-based probe ISG15-Dha(dehydroalanine) through protein semi-synthesis. In vitro crosslinking and cell lysate proteomic profiling experiments showed that this probe can sequentially capture ISG15 conjugating enzymes including E1 enzyme UBA7, E2 enzyme UBE2L6, E3 enzyme HERC5, the previously known ISG15 deconjugating enzyme(USP18), as well as some other enzymes(USP5 and USP14) which we additionally confirmed to impart deISGylation activity. Collectively, ISG15-Dha provides a new tool that can simultaneously capture ISG15 conjugating and deconjugating enzymes for biochemical or pharmacological studies.

Design and synthesis of biotinylated dimethylation of alkannin oxime derivatives

DMAKO-05,a novel dimethylation of alkannin oxime derivative,exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colorectal carcinoma and melanoma.However,its potent cytotoxicity is not closely associated with reactive oxygen species（ROS） and bioreductive alkylation.Its specific antitumor target（s） has still remained elusive.To recognize the molecular target（s） of DMAKO-05 and its analogs,four biotinylated DMAKO derivatives were designed and prepared.The biotin moiety was successfully introduced in the molecule through a modified Mitsunobu reaction,which kept its anticancer activity.Moreover,the cellbased investigation demonstrated that replacement of the linker C4 chain with another alkyl chain（C6 or C8） gave rise to the enhancement of cytotoxicity.Among these biotinyl derivatives,both compound 16 and 8c exhibited more potent anticancer activity than DMAKO-05 against MCF-7 cells and were comparatively effective to alkannin toward HCT-15 cells.As expected,they might be thought as ideal chemical probes.Collectively,our present work could provide an available approach for the identification of the potential antineoplastic target（s） of DMAKO derivatives.