To accelerate research on adversarial examples and robustness of machine learning classifiers, Google Brain organized a NIPS 2017 competition that encouraged researchers to develop new methods to generate adversarial examples as well as to develop new ways to defend against them. In this chapter, we describe the

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The heterodimerized transcription factors CLOCK-BMAL1 regulate the cardiomyocyte circadian rhythms. The L-type calcium currents play important role in the cardiac electrogenesis and arrhythmogenesis. Whether and how the CLOCK-BMAL1 regulate the cardiac L-type calcium channels are yet to be determined. The functions of the L-type calcium channels were evaluated with patch clamping techniques. Recombinant adenoviruses of CLOCK and BMAL1 were used in the expression experiments. We reported that the expressions and functions of CACNA1C (the α-subunit of the L-type calcium channels) showed circadian rhythms, with the peak at zeitgeber time 3 (ZT3). The endocardial action potential durations 90 (APD90) were correspondingly longer at ZT3. The protein levels of the phosphorylated Akt at threonine 308 (pAkt T308) also showed circadian rhythms. Overexpressions of CLOCK-BMAL1 significantly reduced the levels of CACNA1C while increasing the levels of pAkt T308 and pik3r1. Furthermore, the inhibitory effects of CLOCK-BMAL1 on CACNA1C could be abolished by the Akt inhibitor MK2206 or the PDK1 inhibitor GSK2334470. Collectively, our findings suggested that the expressions of the cardiac CACNA1C were under the CLOCK-BMAL1 regulation, probably through the PI3K-Akt signal pathway.

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Objective Anti-DFS70 antibodies correlating with the nuclear dense fine speckled (DFS) pattern in the HEp-2 indirect immunofluorescence assay (IFA) are less common in patients with systemic autoimmune rheumatic disease (SARD) than in healthy subjects and their clinical associations remain elusive. We hosted a multi-center HEp-2 IFA training program to improve the ability of clinical laboratories to recognize the DFS pattern and to investigate the prevalence and relevance of anti-DFS70 antibodies. Methods DFS pattern sera identified by HEp-2 IFA in 29 centers in China were redirected to a central laboratory for anti-DFS70 testing by line immunoblot assay (LIA), enzyme-linked immunosorbent assay (ELISA), and IFA with HEp-2 ELITE/DFS70-KO substrate. Anti-extractable nuclear antigen antibodies were measured by LIA and the clinical relevance was examined in adult and pediatric patients. Results HEp-2 IFA positive rate and DFS pattern in positive sera were 36.2% (34,417/95,131) and 1.7% (582/34,417) in the patient cohort, and 10.0% (423/4,234) and 7.8% (33/423) in a healthy population, respectively. Anti-DFS70 prevalence among sera presenting the DFS pattern was 96.0, 93.7, and 49.6% by ELISA, LIA, and HEp-2 ELITE, respectively. 15.5% (52/336) of adult and 50.0% (20/40) of pediatric anti-DFS70 positive patients were diagnosed with SARD. Diseases most common in anti-DFS70 positive patients were spontaneous abortion (28.0%) in adults and juvenile idiopathic arthritis (22.5%) in pediatric patients. Conclusion Accurate DFS pattern identification increased the detection rate of anti-DFS70 antibodies by ELISA and LIA. Anti-DFS70 antibodies are remarkably high in cases of spontaneous abortion and in pediatric SARD patients, but not prevalent in adult SARD patients.