We present a practical verification method for safety analysis of the autonomous driving system (ADS). The main idea is to build a surrogate model that quantitatively depicts the behavior of an ADS in the specified traffic scenario. The safety properties proved in the resulting surrogate model apply to the original ADS with a probabilistic guarantee. Given the complexity of a traffic scenario in autonomous driving, our approach further partitions the parameter space of a traffic scenario for the ADS into safe sub-spaces with varying levels of guarantees and unsafe sub-spaces with confirmed counter-examples. Innovatively, the partitioning is based on a branching algorithm that features explainable AI methods. We demonstrate the utility of the proposed approach by evaluating safety properties on the state-of-the-art ADS Interfuser, with a variety of simulated traffic scenarios, and we show that our approach and existing ADS testing work complement each other. We certify five safe scenarios from the verification results and find out three sneaky behavior discrepancies in Interfuser which can hardly be detected by safety testing approaches.

The non-archosauriform archosauromorph Dinocephalosaurus orientalis was first described from the Upper Member of the Guanling Formation (late Anisian, Middle Triassic) of Guizhou Province by Li in 2003 on the basis of a complete articulated skull and the first three cervical vertebrae exposed in dorsal to right lateral view. Since then, additional specimens have been discovered in southwestern China. Here, five newly discovered specimens are described for the first time, and redescriptions of the holotype IVPP V13767 and another referred specimen, IVPP V13898, are provided. Together, these permit the description of the complete skeleton of this remarkable long-necked marine reptile. The postcranial skeleton is as much as 6 metres long, and characterised by its long tail and even longer neck. The appendicular skeleton exhibits a high degree of skeletal paedomorphosis recalling that of many sauropterygians, but the skull and neck are completely inconsistent with sauropterygian affinities. The palate does not extend back over the basisphenoid region and lacks any development of the closed condition typical of sauropterygians. The arrangement of cranial elements, including the presence of narial fossae, is very similar to that seen in another long-necked archosauromorph, Tanystropheus hydroides, which at least in part represents a convergence related to an aquatic piscivorous lifestyle. The long and low cervical vertebrae support exceptionally elongate cervical ribs that extend across multiple intervertebral joints and contribute to a ‘stiffening bundle of ribs’ extending along the entire ventral side of the neck, as in many other non-crocopodan archosauromorphs. The functional significance of the extraordinarily elongate neck is hard to discern but it presumably played a key role in feeding, and it is probably analogous to the elongate necks seen in pelagic, long-necked plesiosaurs. Dinocephalosaurus orientalis was almost certainly a fully marine reptile and even gave birth at sea.

Considering the influence of body’s growth and development on thyroid volume (TVOL), whether five existed corrected methods could be applied to correct TVOL remains unclear, in terms of Chinese children’s increased growth and development trends. This study aimed to compare the applicability of five correction methods: Body Surface Area corrected Volume (BSAV), Body Mass Indicator corrected Volume (BMIV), Weight and Height corrected Volume Indicator (WHVI), Height corrected Volume Indicator 1 (HVI1) and Height corrected Volume Indicator 2 (HVI2) and to establish the reference values for correction methods. The data of Iodine Nutrition and Thyroid Function Survey were used to analyse the differences in TVOL between normal and abnormal thyroid function children. Data of National Iodine Deficiency Disorders Survey were used to compare five correction methods and to establish their reference values. The median urinary iodine concentrations of children surveyed were 256·1 μg/l in 2009 and 192·6 μg/l in 2019. No significant difference was found in TVOL and thyroid goitre rate between children with normal and abnormal thyroid function. In the determination of goitre, HVI1, HVI2, BSAV and BMIV all showed high agreement with TVOL, while the area under the receiver operating characteristic curve (AUC) of WHVI was relatively low for children aged 8 (AUC = 0·8993) and 9 (AUC = 0·8866) years. Most differences of TVOL between light and heavy weight, short and tall height children can be eliminated by BSAV. BSAV was the best corrected method in this research. Reference values were established for corrected TVOL in Chinese children aged 8–10 years by sex.

Excessive iodine can lead to goiters. However, the relationship between the water iodine concentration (WIC) and goiter rate (GR) is unclear. This study aims to explore the factors that influence children’s GR in areas with high WIC and analyse the threshold value of the GR increase associated with the WIC. According to the monitoring of the areas with high WIC in China in 2018–2020, a total of 54 050 children in eight high water iodine provinces were chosen. Drinking water, urine and edible salt samples of children were collected. The thyroid volume (Tvol) was measured. A generalised additive model (GAM) was used to analyse the relationship between the WIC and GR in children. Among the 54 050 children in areas with high WIC, the overall GR was 3·34 %, the median of water iodine concentration was 127·0 µg/l, the median of urinary iodine concentration was 318 µg/l and the non-iodised salt coverage rate (NISCR) was 63·51 %. According to the GAM analysis results, water iodine and urinary iodine are factors that influence the Tvol and GR, while the NISCR affects only the GR. When the WIC was more than 420 µg/l or the urinary iodine concentration was more than 800 µg/l, the GR increased rapidly. When the NISCR reached more than 85 %, the GR was the lowest. Thus, in areas with high WIC, WIC more than 420 µg/l may increase the risk of goiter, and the NISCR should be increased to over 85 % to avoid goiters in children.

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12 237 non-T2DM participants aged over 18 years from the Rural Chinese Cohort Study of 2007–2008 were included at baseline and followed up during 2013–2014. The cox proportional hazards regression was used to calculate hazard ratios (HR) and 95 % CI for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6·01 (95 % CI 5·09, 6·06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR for the highest v. lowest METS-VF quartile was 5·97 (95 % CI 4·28, 8·32), with a per 1-sd increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose–response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0·0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age or BMI.

The policy of Universal Salt Iodisation (USI) could reduce population’s thyroid volume (TVOL) in iodine deficiency areas. Conversely, the improved growth and developmental status of children might increase the TVOL accordingly. Whether the decreased TVOL by USI conceals the increase effect of height and weight on TVOL is unclear. The aim of this study was to analyse the association between height, weight, iodine supplementation and TVOL. Five national Iodine Deficiency Disorder surveys were matched into four pairs according to the purpose of analysis. County-level data of both detected by paired surveys were incorporated; 1:1 random pairing method was used to match counties or individuals. The difference of TVOL between different height, weight, different iodine supplementation measures groups and the association between TVOL and them were studied. The mean height and weight of children aged 8–10 years increased from 129·9 cm and 26·9 kg in 2002 to 136·2 cm and 32·1 kg in 2019, while the median TVOL decreased from 3·10 ml to 2·61 ml. Iodine supplementation measures can affect TVOL; after excluding iodine effects, the median TVOL was increased with the height and weight. On the other side, after excluding the influence of height and weight, the median TVOL remained decreased. Only age, weight and salt iodine were significantly associated with TVOL in multiple linear models. Development of height and weight in children is the evidence of improved nutrition. The decreased TVOL caused by iodised salt measures conceals the increase effect of height and weight on TVOL. Age, weight and salt iodine affect TVOL significantly.

Time-restricted feeding (TRF) confers protection against nutritional challenges that predispose obesity and metabolic risks through involvement of circadian locomotor output cycles protein kaput genes and gut microbiome, but the underlying mechanism is not clearly understood. Therefore, the present study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n 56; non-TRF, n 24) of male adults were enrolled. The TRF group provided blood at pre-TRF and post-TRF, while non-TRF one time after 25 d of trial. Serum lipid and liver profiles were determined. Real time-PCR was applied for circadian and inflammatory gene expression. The 16S rRNA genes were sequenced on the Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In the TRF group, gut microbial richness was significantly enhanced, with enrichment of Prevotellaceae and Bacteroideaceae. TRF enhanced circadian gene expression probably by activation of sirtuin-1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidaemia, as it regulates circadian rhythm associated with gut microbiome modulation.

This research paper addresses the hypothesis that Septin6 is a key regulatory factor influencing amino acid (AA)-mediated cell growth and casein synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were treated with absence of AA (AA−), restricted concentrations of AA (AAr) or normal concentrations of AA (AA+) for 24 h. Cell growth, expression of CSN2 and Septin6 were increased in response to AA supply. Overexpressing or inhibiting Septin6 demonstrated that cell growth, expression of CSN2, mTOR, p-mTOR, S6K1 and p-S6K1 were up-regulated by Septin6. Furthermore, overexpressing or inhibiting mTOR demonstrated that the increase in cell growth and expression of CSN2 in response to Septin6 overexpression were inhibited by mTOR inhibition, and vice versa. Our hypothesis was supported; we were able to show that Septin6 is an important positive factor for cell growth and casein synthesis, it up-regulates AA-mediated cell growth and casein synthesis through activating mTORC1 pathway in DCMECs.

OBJECTIVES/SPECIFIC AIMS: MicroRNAs (miRNA) affect transcription of a number of genes involved in the development and progression of diabetic nephropathy (DN), and have become attractive therapeutic targets and biomarkers. Elevated renal gluconeogenesis, fibrosis, and albuminuria are early markers of incipient DN. Recent studies report that renal miRNA-451 may protect against DN and reduce renal gluconeogenesis in rodent models. MiRNA-451 is thought to act by targeting select factors resulting from disrupted insulin and growth factor signaling and the mechanistic-target of rapamycin (mTOR) in early DN. This study aimed to elucidate the role of miRNA-451 in the development and progression of DN. METHODS/STUDY POPULATION: To further elucidate the role of miRNA-451 in DN, we placed male insulin-resistant, TALLYHO/Jng mice on a high-fat diet (60% kCal). The mice were divided into 2 treatment groups and received 8 consecutive weekly intraperitoneal injections of locked nucleic acid (LNA) miR-451-inhibitor or LNA-scrambled compound (2 mg/kg·bw; n=8/treatment). Mice were euthanized after 12 weeks (4 weeks sans injections) and kidneys, liver, pancreas and abdominal adipose tissue were harvested for analysis. RESULTS/ANTICIPATED RESULTS: Renal homogenate expression of miRNA-451 was drastically reduced in inhibitor-treated mice (~6-fold) in comparison with scramble-treated mice. Western blotting of cortex homogenates for indicators of fibrosis and targets of miRNA-451 revealed a significant reduction in collagen IV (marker of epithelial integrity) in inhibitor-treated mice. In addition, metalloproteinase type 9 (MMP9, a known type IV collagenase), YWHAZ (a scaffolding protein and known target of miR-451), mTOR, and fructose bisphosphatase (FBP1, a rate-limiting gene in gluconeogenesis) were significantly increased in this group in comparison to scramble-treated mice. However, no differences were found in protein levels for glucose-6-phosphatase (G-6-Pase) or phosphoenolpyruvate (PEPCK), 2 additional gluconeogenic rate-limiting genes. MiRNA-451 antagonist did not significantly affect final body weight or blood glucose; however, mean blood sodium concentrations were slightly, but significantly higher (2%) in the LNA-inhibitor treated group (when compared with the scramble-treated group). No differences in blood potassium or chloride were found. Anion gap was 90% higher in the LNA-inhibitor treated group when compared with scramble-treated mice. No differences in urinary albumin to creatinine ratio were found between the two treatment groups. However, Masson Trichrome scoring revealed a 59% increase in fibrosis in inhibitor-treated mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these findings support a potentially protective role of miRNA-451 in attenuating signaling via mTOR that may alter both renal gluconeogenic potential (contributing to the diabetic phenotype) and activation and progression of renal fibrosis. Therapies to enhance miRNA-451 signaling may be beneficial to reduce renal pathology associated with DN.

A hypoeutectic CoCrFeNiNbχ system was synthesized to investigate the effect of Nb content on the thermal stability, mechanical properties, and corrosion behaviors. The hypoeutectic CoCrFeNiNbχ alloy, which contained the Laves phase, possessed two-phase eutectic structures. The elevated temperature may have an impact on the stability of the Laves phase. Nanoindentation measurements showed that the Laves phase is much harder than the FCC phase, which could be confirmed by the shallower maximum penetration depth in the typical P–h curve. Furthermore, the plasticity of the Laves phase was characterized by nanoindentation measurements. Compared with the FCC phase, the activation energy of dislocation nucleation in the Laves phase is much higher due to the large atomic size difference and the phase difference. Corrosion and passivation behaviors of CoCrFeNiNbχ were investigated in 3.5% NaCl solution. All the alloys exhibited spontaneous passivity and low current densities in 3.5% NaCl solution. Furthermore, the corrosion potential increased with the increasing Nb content, which indicated that the corrosion resistance enhanced with a higher Nb content.

In this paper, both the proportional derivative feedback control and variable-structure sliding mode control approaches based on dual numbers are presented to design space flyaround and in-orbit inspection missions. Dual-number-based spacecraft kinematics and dynamics models are formulated. The integrated translational and rotational motions can be described in one compact expression, and the mutual coupling effect can be considered. A space flyaround and in-orbit inspection mission model based on dual numbers is derived. Both proportional derivative feedback control and variable-structure sliding mode control laws are designed using dual numbers. Simulation results indicate that both the proposed control system can provide high-precision control for relative position and attitude. Of the two systems, the variable-structure sliding mode control system performs the best.

To improve the antimicrobial properties of ZnO, ZnO-supported 13X zeolite (X-ZnO) was prepared via the facile chemical method. Antimicrobial activities of X-ZnO and ZnO were tested against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. X-ZnO showed noticeable antimicrobial activities against E. coli and S. aureus under visible light conditions, especially against E. coli. The minimum inhibitory concentration (MIC) of X-ZnO against E. coli was 0.12–0.24 mg/mL. However, there were still much bacteria alive in the nano-ZnO suspensions at the same concentration. To elucidate the antimicrobial activities of X-ZnO, the average concentration of the total reactive oxygen species (ROS) and Zn2+ ions released from X-ZnO and nano-ZnO were quantitatively analyzed. The obtained results indicated that the average concentration of ROS produced by supported ZnO was much higher than that of nano-ZnO. And the released Zn2+ ions from X-ZnO and nano-ZnO suspensions were much lower than the MIC of Zn2+. Thus, it is believed that the production of ROS in X-ZnO and nano-ZnO suspensions resulted in the difference of antibacterial activities.

Early life is considered a critical period for determining long-term metabolic health. Postnatal over-nutrition may alter glucocorticoid (GC) metabolism and increase the risk of developing obesity and metabolic disorders in adulthood. Our aim was to assess the effects of the dose and timing of a fish oil diet on obesity and the expression of GC-activated enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD1) in postnatal overfed rats. Litter sizes were adjusted to three (small litter (SL)) or ten (normal litter) rats on postnatal day 3 to induce overfeeding or normal feeding. The SL rats were divided into three groups after weaning: high-dose fish oil (HFO), low-dose fish oil (LFO) and standard-diet groups. After 10 weeks, the HFO diet reduced body weight gain (16 %, P<0·05), improved glucose intolerance and decreased hyperlipaemia levels (P<0·05) in SL rats, but the LFO diet did not have any effect on the same rats. Moreover, we chose postnatal week 3 (W3), 6 (W6) and 8 (W8) as the intervention time points at which to begin the 10-week HFO diet, and found that the HFO diet improved glucose utilisation and lipid metabolism at all time points. However, body weight of SL rats was reversed to normal levels by the post-weaning intervention (461 (sem 9·1) v. 450 (sem 2·0)). 11β-HSD1 mRNA expression in the adipose tissue (49 (sem 7·5) v. 161 (sem 18·3), P<0·05) and hepatic tissue (11 (sem 0·9) v. 16 (sem 1·5), P<0·05) was decreased by the HFO diet at W3, but not at W6 or W8 (P>0·05). In conclusion, the post-weaning HFO diet could reverse adverse outcomes and decrease tissue GC activity in postnatal overfed rats.

The aim of the present work was to determine maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP) in twin pregnancies. All twin pregnancies delivered above 28 gestational weeks in West China Second University Hospital from January 2013 to May 2015 were included. Data on maternal demographics and obstetric complications together with fetal outcomes were collected. The risk of adverse maternal and fetal outcomes were determined in relation to ICP by crude odds ratios (OR) and adjusted ORs (aOR) with 95% confidence intervals (CI). Subgroup analysis concentrated on the effect of assisted reproductive technology (ART), ICP severity, and onset time. A total of 1,472 twin pregnancies were included, of which 362 were cholestasis patients and 677 were conceived by ART. Higher rates of preeclampsia (aOR 1.96; 95% CI 1.35, 2.85), meconium-stained amniotic fluid (aOR 3.10; 95% CI 2.10, 4.61), and preterm deliveries (aOR 3.20; 95% CI 2.35, 4.37) were observed in ICP patients. Subgroup analysis revealed higher incidences of adverse outcomes in severe and early onset ICP groups. In conclusion, adverse maternal and fetal outcomes were strongly associated with ICP in twin patients. Active management and close antenatal monitoring are needed, especially in the early onset and severe groups.