Generalized Anomaly Detection

We study anomaly detection for the case when the normal class consists of more than one object category. This is an obvious generalization of the standard one-class anomaly detection problem. However, we show that jointly using multiple one-class anomaly detectors to solve this problem yields poorer results as compared to training a single one-class anomaly detector on all normal object categories together. We further develop a new anomaly detector called DeepMAD that learns compact distinguishing features by exploiting the multiple normal objects categories. This algorithm achieves higher AUC values for different datasets compared to two top performing one-class algorithms that either are trained on each normal object category or jointly trained on all normal object categories combined. In addition to theoretical results we present empirical results using the CIFAR-10, fMNIST, CIFAR-100, and a new dataset we developed called RECYCLE.Comment: 13 page

Facile synthesis of chitosan-capped ZnS quantum dots as an eco-friendly fluorescence sensor for rapid determination of bisphenol A in water and plastic samples

This paper describes a novel eco-friendly fluorescence sensor for determination of bisphenol A (BPA) based on chitosan-capped ZnS quantum dots (QDs). By using safe and inexpensive materials, nontoxic ZnS QDs were synthesized via an environment-friendly method using chitosan as a capping agent. The as-prepared ZnS QDs exhibited characteristic absorption (absorbance edge at 310 nm) and emission (maxima at 430 nm) spectra with a relatively high fluorescence quantum yield of 11.8%. Quantitative detection of BPA was developed based on fluorescence quenching of chitosan-capped ZnS QDs with high sensitivity and selectivity. Under optimal conditions, the fluorescence response of ZnS QDs was linearly proportional to BPA concentration over a wide range from 0.50 to 300 mu g L-1 with a detection limit of 0.08 mu g L-1. Most of the potentially coexisting substances did not interfere with the BPA-induced quenching effect. The proposed analytical method for BPA was successfully applied to water and plastic real samples. The possible quenching mechanism is also discussed

A multimechanistic antibody targeting receptor-binding sites potently cross-protects against influenza B viruses

流感病毒HA是研制流感药物和流感疫苗的重要靶标，但HA具有高度变异性，如何在高变异HA中找到不变之处，即高度保守表位，是研制流感特效药物和广谱疫苗的关键。近年来国外报道的流感HA广谱中和单抗的识别位点均在较为保守的HA茎部区，而针对流感病毒与细胞受体结合部位的HA头部区尤其是RBS区，一直未能发现广谱中和抗体。夏宁邵教授团队通过探索多种免疫策略和筛选策略，成功筛选出一株广谱中和单抗12G6，识别一个位于HA头部RBS上的全新保守性表位。体外实验显示12G6人源化改造的C12G6抗体能高效中和1940-2016年间世界各地历年流行的代表三个遗传变异亚系的18个乙型流感病毒代表株对细胞的感染，并能保护小鼠致死性感染，治疗效果显著优于已报道的代表性抗体以及抗流感药物；C12G6与“达菲”联合用药具有明显的协同效果。此外，雪貂感染模型的预防和治疗效果进一步证实了C12G6作为抗体药物的治疗潜能。研究还显示该表位是病毒感染复制的关键表位，该位点的突变会造成病毒毒力显著下降。最后，研究揭示了C12G6通过五种不同的抗病毒作用机制发挥作用，提示其高效的抗病毒活性得益于多机制协同效应，这也是目前国内外第一次发现一个流感抗体能通过如此全面的抗病毒机制发挥作用。 该发现为研制能抵抗各种变异株的乙型流感特效治疗药物和通用疫苗带来新希望。 该研究工作依托分子疫苗学和分子诊断学国家重点实验室（厦门大学）、国家传染病诊断试剂与疫苗工程技术研究中心、厦门大学养生堂生物药物联合实验室完成。陈毅歆副教授、夏宁邵教授为该研究论文的共同通讯作者。在读博士研究生沈晨光、陈俊煜、李睿、王国松和硕士研究生张梦娅等为共同第一作者。【Abstract】Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a new approach for combating influenza. We describe the generation and characterization of a chimeric monoclonal antibody, C12G6, that cross-neutralizes representative viruses spanning the 76 years of influenza B antigenic evolution since 1940, including viruses belonging to the Yamagata, Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage hemagglutination inhibition activity against influenza B viruses and has higher potency and breadth of neutralization when compared to four previously reported influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral effect when administered in combination with oseltamivir. Epitope mapping indicated that C12G6 targets a conserved epitope that overlaps with the receptor binding site in the HA region of influenza B virus, indicating why it neutralizes virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B viruses via multiple mechanisms, including preventing viral entry, egress, and HA-mediated membrane fusion and triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore a promising candidate for the development of prophylactics or therapeutics against influenza B infection and may inform the design of a truly universal influenza vaccine.This research was supported by grants from the National Natural Science Foundation of China (31670934 and 81371817), the Ministry of Science and Technology of the People’s Republic of China (2011ZX09102-009-12 and 2012DFH30020), the Research Grants Council of the Hong Kong Special Administrative Region (7629/13M, 17103214, and 17154516), and a sponsored research agreement from Sanofi Pasteur. 研究工作得到了香港大学新发传染病国家重点实验室和赛诺菲巴斯德公司的技术支持和帮助，获得国家自然科学基金、新药创制国家科技重大专项、科技部对港科技合作项目等课题资助

Highly sensitive detection of organophosphorus pesticides represented by methamidophos via inner filter effect of Au nanoparticles on the fluorescence of CdTe quantum dots

A sensitive fluorescence detection method of organophosphate pesticides (OPs) represented by methamidophos was developed using the inner filter effect (IFE) of Au nanoparticles (AuNPs) on CdTe quantum dots (QDs). The fluorescence of CdTe QDs was remarkably quenched with the presence of AuNPs via IFE. Acetylcholinesterase (AChE) catalyzed the hydrolysis of acetylthiocholine into thiocholine, which could induce the aggregation of AuNPs and decrease their characteristic absorption, making IFE-decreased fluorescence of CdTe QDs recovered. OPs can inhibit the activity of AChE, thus preventing the aggregation of AuNPs and the fluorescence recovery of CdTe QDs. Therefore, the IFE of fluorescence between AuNPs and CdTe QDs could convert the absorption signal to fluorescence signal, which improved the detection sensitivity of OPs in vegetables. Under the optimum conditions, the response was linearly proportional to the concentration of methamidophos in the range of 0.06 similar to 0.78 mg/kg with a detection limit of 2 mu g/kg (3 sigma) which was superior to the method of GB/T 5009.199-2003. The proposed assay exhibited good reproducibility and accuracy, providing a simple and rapid method for the screening of OPs

Sensitive fluorescent detection of carbamate pesticides represented by methomyl based on the inner filter effect of Au nanoparticles on the fluorescence of CdTe quantum dots

Based on the inner filter effect (IFE) of Au nanoparticles (AuNPs) on the fluorescence of CdTe quantumdots (QDs), a novel fluorescence method for the rapid assay of carbamate pesticides has been developed. The fluorescence of CdTe QDs was remarkably quenched in the presence of AuNPs via IFE. Acetylcholinesterase (AChE) catalyzed the hydrolysis of acetylthiocholine into thiocholine, which could induce the aggregation of AuNPs and decrease their characteristic absorption, thereby recovering the IFE-decreased fluorescence of the CdTe QDs. Carbamate pesticides can inhibit the activity of AChE, thus preventing the aggregation of AuNPs and the fluorescence recovery of CdTe QDs. Therefore, the IFE of the fluorescence between AuNPs and CdTe QDs could convert the absorption signal to a fluorescence signal, which improved the detection sensitivity of carbamate pesticides in vegetables. The calibration curve for methomyl was established in the range of 0.017-0.5 mu g mL(-1) with a detection limit of 0.011 mu g mL(-1) (S/N=3) which is superior to the HPLC coupled with UV detection method. This method was successfully carried out for the assessment of methomyl in vegetables, and has many advantages such as high sensitivity, low cost and rapidity in comparison with traditional methods

Inhibition of fatty acid synthase supresses osteosarcoma cell invasion and migration

Background : Fatty acid synthase (FASN) is overexpressed in a variety of human cancers, and may be involved in cancer metastasis. Hence, the strategies targeted on FASN may have therapeutic potential for treating cancer metastasis. Objectives : The aim of this study is to investigate the correlation of FASN expression with metastasis in human osteosarcoma. Materials and Methods : Human osteosarcoma cell lines U2-OS and osteosarcoma biopsy specimens were employed in this study. The expression of FASN protein in osteosarcoma specimens was detected by IHC (immunohistochemistry) and the relationship with metastasis was analyzed. We performed the cerulenin, an inhibitor of FASN, to inhibit FASN expression in U2-OS cells. Western blot and RT-PCR were performed to investigate the expression of FASN in U2-OS cells. Cells mobility was detected by wound healing and Transwell assays. Results : Results showed that the FASN expression level in the cases with pulmonary metastases was significantly higher than in those without metastasis. In vitro, the invasion and migration of U2-OS cells were suppressed by inhibiting FASN. Our findings suggested that FASN may be involved in osteosarcoma metastasi

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research