ACHIEVING OPTIMAL ADVERSARIAL ACCURACY FOR ADVERSARIAL DEEP LEARNING USING STACKELBERG GAMES

The purpose of adversarial deep learning is to train robust DNNs against adversarial attacks,and this is one of the major research focuses of deep learning.Game theory has been used to answer some of the basic questions about adversarial deep learning,such as those regarding the existence of a classifier with optimal robustness and the existence of optimal adversarial samples for a given class of classifiers.In most previous works,adversarial deep learning was formulated as a simultaneous game and the strategy spaces were assumed to be certain probability distributions in order for the Nash equilibrium to exist.However,this assumption is not applicable to practical situations.In this paper,we give answers to these basic questions for the practical case where the classifiers are DNNs with a given structure;we do that by formulating adversarial deep learning in the form of Stackelberg games.The existence of Stackelberg equilibria for these games is proven.Furthermore,it is shown that the equilibrium DNN has the largest adversarial accuracy among all DNNs with the same structure,when Carlini-Wagner s margin loss is used.The trade-off between robustness and accuracy in adversarial deep learning is also studied from a game theoretical perspective.

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

AIMTo investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODSAdult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTSCirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM P = 0.01) for infection. A very low QFM P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSIONQFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.

Chemo–immunotherapy for chemo-resistance and metastasis of triple-negative breast cancer by combination of iron-oxide nanoparticles and dual-targeting doxorubicin liposomes

Triple-negative breast cancer(TNBC)lacks specific regimens for targeted therapy.Repeat chemotherapy promotes the evolution of TNBC into highly chemo-resistant tumors that metastasize to multiple organs simultaneously.Herein,polyacrylic acid-coated ultrasmall superparamagnetic iron-oxide nanoparticles(PAA@IONs)and dual-targeting doxorubicin liposomes achieved chemo–immunotherapy through intermittent administration.They inhibited tumor-drug resistance and multiorgan-specific metastasis significantly by targeting tumors and the microenvironment.We deciphered an immunosuppressive pre-metastatic niche and discovered that PAA@IONs could target tumors,tumor-draining lymph nodes(TDLNs),the liver,bone,and lungs.They promoted the polarization of macrophages into M1 macrophages in these organs and tissues.This action remodeled the immunosuppressive microenvironment and induced a sustained immune response,thereby reducing organ-specific metastasis.Overcoming the disadvantages of doxorubicin-induced cardiotoxicity as well as low tumor specificity,dual peptide-modified liposomes could target CD206 and CD13 simultaneously,and reverse chemo-resistance.These properties resulted in a significant decrease in the numbers of myeloid-derived suppressor cells(MDSCs)and cancer stem cells(CSCs)in the liver,lungs,and bone,thereby reducing protein expression of Ki-67 in TDLNs,and dramatically increasing the number of cluster of differentiation(CD)8+T cells and CD8+T cell/T-regulatory-cell ratio in tumors and TDLNs(P<0.0001).Compared with the control(P<0.05 and P<0.01,respectively)or free drug(P<0.0001 and P<0.01,respectively),multi-organ metastases were suppressed significantly,tumor-growth rate reduced,and survival prolonged.Our drug-delivery system overcame TNBC chemo-resistance and inhibited multiorgan-specific metastases.It circumvents the lack of effective therapeutic targets,the problem of patient selection due to a low mutation rate,and can simultaneously offer the possibility of avoiding surgery and considerable postoperative complications.

间充质干细胞治疗新型冠状病毒肺炎的研究进展与应用前景

当前新型冠状病毒肺炎疾病已在全球大规模蔓延,严重危害人类的健康。新病毒感染性强并且感染后重症患者病死率较高,目前尚无有效的特异性治疗药物,因此亟待寻找安全有效的治疗方法。间充质干细胞(Mesenchymal stem cells,MSCs)具有强大的免疫调节和组织损伤修复与再生的生物学功能,因此作为一种干细胞疗法有潜力降低新冠肺炎重症患者的组织损伤和死亡率。目前,我国和国外多家研究机构已启动多项MSCs治疗新型冠状病毒肺炎的相关临床研究项目,已初步证实该疗法的安全性和有效性,因此具有非常良好的临床治疗前景。

A comparative study of assembly and disassembly process of dimeric and monomeric cyanine dyes with DNA templates

Cyanine dyes have attracted more and more interest due to their controllable assembly and disassembly process with biomolecular templates. The self-assembly of cyanine dye not only depend on the environment, but also on their structures. Here, we report assembly and disassembly of two cyanine dyes,a dimeric cyaine dye(TC-P4) and its corresponding monomer(TC). In PBS, these dyes could form aggregates. The parallel c-myc G-quadruplex as a template causes the transformation of TC-P4 from Haggregates to dimer and monomer; while duplex and single-stranded DNAs could not. The interaction between these DNAs motifs and TC could all induce the appearance of monomer band. Parallel c-myc Gquadruplex could enhance the fluorescence intensity of TC-P4 and TC. The self-assembly and disassembly of TC and TC-P4 could be regulated and used as probes for G-quadruplex recognition from duplex and single-stranded DNAs in solution.