Masking: A New Perspective of Noisy Supervision

It is important to learn various types of classifiers given training data with noisy labels. Noisy labels, in the most popular noise model hitherto, are corrupted from ground-truth labels by an unknown noise transition matrix. Thus, by estimating this matrix, classifiers can escape from overfitting those noisy labels. However, such estimation is practically difficult, due to either the indirect nature of two-step approaches, or not big enough data to afford end-to-end approaches. In this paper, we propose a human-assisted approach called Masking that conveys human cognition of invalid class transitions and naturally speculates the structure of the noise transition matrix. To this end, we derive a structure-aware probabilistic model incorporating a structure prior, and solve the challenges from structure extraction and structure alignment. Thanks to Masking, we only estimate unmasked noise transition probabilities and the burden of estimation is tremendously reduced. We conduct extensive experiments on CIFAR-10 and CIFAR-100 with three noise structures as well as the industrial-level Clothing1M with agnostic noise structure, and the results show that Masking can improve the robustness of classifiers significantly.Comment: NIPS 2018 camera-ready versio

Molecular basis of porcine reproductive and respiratory syndrome virus-mediated innate immune suppression

Porcine reproductive and respiratory syndrome (PRRS) is an emerged and re-emerging swine disease featured by severe reproductive losses, post-weaning pneumonia, and increased mortality. During infection of PRRS virus, poor induction of pro-inflammatory cytokines and type I IFNs are observed, and PRRSV seems to have a capacity to escape the immune surveillance for survival. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral IFN antagonist, and nsp1 has been shown to degrade the CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus resulting in the suppression of IFN production. Nsp1 is auto-processed into nsp1α and nsp1β subunits, and individual subunits (nsp1α and nsp1β) of nsp1 suppress type I IFN production. In the present study, the nsp1α subunit was shown to be responsible for CBP degradation. PRRSV-nsp1β was mainly distributed in the nucleus and played roles for host cell mRNA nuclear retention leading to subversion of host protein synthesis and suppression of type I IFN production. This study was expanded to other member viruses in the family Arteriviridae, and all subunits of arterivirus nsp1 presented the IFN suppressive activity. Similar to PRRSV-nsp1α, CBP degradation was evident in cells expressing LDV-nsp1α and SHFV-nsp1γ. PRRSV-nsp1β-mediated mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β, but for EAV-nsp1. To study the structure function of PRRSV-nsp1 and its IFN antagonism, motifs for PLP1α (papain-like proteinase 1α), ZF1 (zinc-finger domain 1), and ZF2 within the nsp1α subunit were individually mutated and the mutant proteins were examined for their IFN suppressive ability. Single or double mutations of C8S, C10S, C25S, and/or C28S for the ZF1 motif impaired the IFN antagonism, demonstrating that ZF1 is the essential element of nsp1α for IFN suppression. The ZF1 mutants did not induce CBP degradation and nor IFN suppression. For nsp1β, a SAP motif was identified with the consensus sequence of 126-LQxxLxxxGL-135 by bioinformatics analysis. Cytoplasmic staining was observed for SAP mutants L126, R129A, L130A, and L135A, and these mutants did not cause the nuclear retention of host cell mRNAs, and were unable to inhibit IFN signaling. Using reverse genetics, SAP mutant viable viruses vK124A, vL126A, vG134A, and vL135A were recovered. nsp1β protein was retained in the cytoplasm in cells infected with vL126A and vL135A. Accordingly, no mRNA nuclear retention was observed in these cells, and also no suppression of IFN production was identified. My study demonstrates nsp1 as the type I IFN antagonist in the family Arteriviridae and the molecular basis for this antagonism

Interfacial energy release rates of SiN/GaAs film/substrate systems determined using a cyclic loading dual-indentation method

Our previous study developed a dual-indentation method for testing the interfacial energy release rate, Gin, of the SiN/GaAs film/substrate systems. However, for the film/substrate systems with relatively high interfacial toughness, the dual-indentation method was unable to generate interfacial delamination. In this study, a cyclic loading dual-indentation method was proposed, in which the first monotonic loading in the dual-indentation method was replaced by cyclic loading. It was demonstrated that cyclic loading was effective at inducing delamination in relatively "tough" SiN/GaAs interfaces that were unable to be delaminated by dual-indentation method. The Gin values obtained from the cyclic loading indentation were in good agreement with those obtained from the dual-indentation method for the less tough interfaces. The delamination mechanism in the cyclic loading indentation was attributed to the hardening effect on the films induced by cyclic loading, permitting sufficient elastic strain energy to be accumulated to initiate the delamination

Selective laser melting of alumina: a single track study

Ceramics-based additive manufacturing is a complex process and the solidification mechanism and microstructural evolution are currently not fully understood. In this work, AlO single tracks were formed using a customised selective laser melting (SLM) system equipped with a high power diode laser. The effects of laser energy density (LED) on geometry, microstructure and micro-mechanical properties of AlO tracks were investigated. To better understand the solidification mechanism, a transient three-dimensional thermal model was developed for predicting the thermal behaviour of the melt pool. The results indicated the use of high LED gave rise to decreased viscosity and surface tension of the molten alumina and led to localized melting of the substrate. Both, in turn, enabled the formation of a continuous solidified track. The solidified tracks were primarily composed of columnar dendrite. When relatively high LED (≥ 25.7 kJ/m) was applied, equiaxed dendrite appeared along the central line near the track surface. The size of dendritic grains decreased with the decreased LED, attributed to the increased cooling rate at solidification interface. The micro-hardness of the solidified track was found to be inversely proportional to the grain size owning to grain boundary strengthening effect

Biogenesis of non-structural protein 1 (nsp1) and nsp1-mediated type I interferon modulation in arteriviruses

AbstractType I interferons (IFNs-α/β) play a key role for the antiviral state of host, and the porcine arterivirus; porcine reproductive and respiratory syndrome virus (PRRSV), has been shown to down-regulate the production of IFNs during infection. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral IFN antagonist, and the nsp1α subunit of nsp1 has been shown to degrade the CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus resulting in the suppression of IFN production. The study was expanded to other member viruses in the family Arteriviridae: equine arteritis virus (EAV), murine lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV). While PRRSV–nsp1 and LDV–nsp1 were auto-cleaved to produce the nsp1α and nsp1β subunits, EAV–nsp1 remained uncleaved. SHFV–nsp1 was initially predicted to be cleaved to generate three subunits (nsp1α, nsp1β, and nsp1γ), but only two subunits were generated as SHFV–nsp1αβ and SHFV–nsp1γ. The papain-like cysteine protease (PLP) 1α motif in nsp1α remained inactive for SHFV, and only the PLP1β motif of nsp1β was functional to generate SHFV–nsp1γ subunit. All subunits of arterivirus nsp1 were localized in the both nucleus and cytoplasm, but PRRSV–nsp1β, LDV–nsp1β, EAV–nsp1, and SHFV–nsp1γ were predominantly found in the nucleus. All subunits of arterivirus nsp1 contained the IFN suppressive activity and inhibited both interferon regulatory factor 3 (IRF3) and NF-κB mediated IFN promoter activities. Similar to PRRSV–nsp1α, CBP degradation was evident in cells expressing LDV–nsp1α and SHFV–nsp1γ, but no such degradation was observed for EAV–nsp1. Regardless of CBP degradation, all subunits of arterivirus nsp1 suppressed the IFN-sensitive response element (ISRE)-promoter activities. Our data show that the nsp1-mediated IFN modulation is a common strategy for all arteriviruses but their mechanism of action may differ from each other

Inducing stable interfacial delamination in a multilayer system by four-point bending of microbridges

The ability to produce stable delamination of thin film multilayer interfaces is a powerful tool for studying the interfacial adhesion within microsystems. In this study, a technique involving the four-point bending of microbridges was applied to initiate stable interfacial delamination within a multilayer system. Microscale pre-notched bridges with clamped-ends were machined into an Al/SiN/GaAs multilayer using focus ion beam milling. A square flat-end indenter was used to induce bending of the bridge by two contact locations. Bridge failure occurred via substrate fracture at the pre-notch, followed by crack deflection, and stable interfacial delamination of the SiN/GaAs interface. Substrate fracture and delamination were identified within the obtained load-displacement curves as a pop-in and region of linear load reduction respectively

Probabilistic Margins for Instance Reweighting in Adversarial Training

Reweighting adversarial data during training has been recently shown to improve adversarial robustness, where data closer to the current decision boundaries are regarded as more critical and given larger weights. However, existing methods measuring the closeness are not very reliable: they are discrete and can take only a few values, and they are path-dependent, i.e., they may change given the same start and end points with different attack paths. In this paper, we propose three types of probabilistic margin (PM), which are continuous and path-independent, for measuring the aforementioned closeness and reweighting adversarial data. Specifically, a PM is defined as the difference between two estimated class-posterior probabilities, e.g., such the probability of the true label minus the probability of the most confusing label given some natural data. Though different PMs capture different geometric properties, all three PMs share a negative correlation with the vulnerability of data: data with larger/smaller PMs are safer/riskier and should have smaller/larger weights. Experiments demonstrate that PMs are reliable measurements and PM-based reweighting methods outperform state-of-the-art methods.Comment: 17 pages, 4 figure

Equine Arteritis Virus Does Not Induce Interferon Production in Equine Endothelial Cells: Identification of Nonstructural Protein 1 as a Main Interferon Antagonist

The objective of this study was to investigate the effect of equine arteritis virus (EAV) on type I interferon (IFN) production. Equine endothelial cells (EECs) were infected with the virulent Bucyrus strain (VBS) of EAV and expression of IFN-β was measured at mRNA and protein levels by quantitative real-time RT-PCR and IFN bioassay using vesicular stomatitis virus expressing the green fluorescence protein (VSV-GFP), respectively. Quantitative RT-PCR results showed that IFN-β mRNA levels in EECs infected with EAV VBS were not increased compared to those in mock-infected cells. Consistent with quantitative RT-PCR, Sendai virus- (SeV-) induced type I IFN production was inhibited by EAV infection. Using an IFN-β promoter-luciferase reporter assay, we subsequently demonstrated that EAV nsps 1, 2, and 11 had the capability to inhibit type I IFN activation. Of these three nsps, nsp1 exhibited the strongest inhibitory effect. Taken together, these data demonstrate that EAV has the ability to suppress the type I IFN production in EECs and nsp1 may play a critical role to subvert the equine innate immune response

Demystifying Assumptions in Learning to Discover Novel Classes

In learning to discover novel classes (L2DNC), we are given labeled data from seen classes and unlabeled data from unseen classes, and we train clustering models for the unseen classes. However, the rigorous definition of L2DNC is unexplored, which results in that its implicit assumptions are still unclear. In this paper, we demystify assumptions behind L2DNC and find that high-level semantic features should be shared among the seen and unseen classes. This naturally motivates us to link L2DNC to meta-learning that has exactly the same assumption as L2DNC. Based on this finding, L2DNC is not only theoretically solvable, but can also be empirically solved by meta-learning algorithms after slight modifications. This L2DNC methodology significantly reduces the amount of unlabeled data needed for training and makes it more practical, as demonstrated in experiments. The use of very limited data is also justified by the application scenario of L2DNC: since it is unnatural to label only seen-class data, L2DNC is sampling instead of labeling in causality. Therefore, unseen-class data should be collected on the way of collecting seen-class data, which is why they are novel and first need to be clustered