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Supplementary methods, tables, figures and legends to figures Supplementary Figure 1. The structure of AB loops for sIFN-I and IFNα-2b and comparison on the sequences for sIFN-I and IFNα-21. Supplementary Figure 2. Quantification of phosphorylaiton of STAT1/3 in Figure 3C Supplementary Figure 3. Analysis of the cell surface IFNAR1 levels in the A549-IFNAR1-KO cell clones by FACS. Supplementary Figure 4. sIFN-I shows potent anti-solid tumor effect in immunocompromised mice models. Supplementary Figure 5. sIFN-I treatment decreases cell proliferation and induces senescence in vivo. Supplementary Figure 6. The antitumor effect of sIFN-I in immunocompetent tumor models. Supplementary Figure 7. FACS analysis of splenocytes from tumor-bearing mice treated with sIFN-I. Supplementary Table 1. Primer sequences used in this study. Supplementary Table 2. Primary antibodies used in this study. Supplementary Table 3. The pharmacokinetic index of human IFNα-2b or sIFN-I administered as in Figure 4B was analyzed by WinNonlin version 6.2 software.

Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I.Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK–STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models.Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK–STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8+ T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice.Conclusions: These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038–49. ©2016 AACR.

Field test and analysis were carried out for dynamic responses on a continuous bridge under open traffic. The inspection, testing and analysis for the tested bridge mainly consist of the measurement of pavement roughness and analysis on power spectral density, the testing and analysis on natural vibration characteristics, the observation of traffic loads under open traffic and the corresponding measurements of dynamic displacement and acceleration on bridge. To determine impact factors in terms of measured dynamic displacement responses, low pass Butterworth filter is used for filtering the dynamic part of measured dynamic displacement and the static extreme values are reserved. Finally, the relationship between impact factors and vehicle weight, vehicle speed is studied. It was found that impact factor tends to decrease with increasing vehicle weight, and integrally speaking, the impact factor increases gradually as the vehicle speed is increased within a wide range.

Firstly, synchronous field measurements were carried out for the road roughness of the left and right wheels to obtain the roughness profile using a high speed laser roadway testing vehicle. Secondly, programming idea of multi-girder vehicle-bridge coupled vibration analysis module was presented briefly. Finally, a three-axle heavy truck crossing a rigid-frame arch bridge was taken as an example, detailed comparing and analyzing was carried out for the influence on the dynamic responses and spectrum characteristics of the vehicle-bridge system from three excitation cases which include using measured road roughness corresponding respectively to left and right wheels, using measured road roughness of left wheels and right wheels simultaneously. The analysis shows that when the differences in road roughness between left and right wheels are significant, the responses computed with inconsistent excitation is smaller than that with both of the latter two excitation cases, and there are some differences between the vertical contact forces of wheels and the spectrum characteristics of the vehicle-bridge system.