Results of dynamic simulation of the lateral stability of a light van when curvilinear movement

The article presents the results of developing a methodology and implementing dynamic modeling in the SolidWorks Motion 2016 software environment for changing the body roll angle of the Gazelle Next van during active maneuvering and turning using a lever-electromagnetic stabilization system in comparison with a lever stabilizer system. A dynamic modeling technique was developed to analyze the change in the roll angle of the Gazelle NEXT all-metal van in the driving mode when turning and intensive maneuvering with a lever and using a lever-electromagnetic stabilization system). As a result of the research, a decrease in the roll angle of the Gazelle Next all-metal van was revealed in driving modes with active maneuvering and cornering using the lever-electromagnetic stabilization system relative to that installed on the example of the Gazelle NEXT — lever. The proposed method of dynamic modeling proved the effectiveness of using a lever-electromagnetic stabilization system when turning and active maneuvering, compared with standard lever stabilizers based on a comparison of the roll angles of the first and second options

Supplementary Material for: Desmosterol in Brain Is Elevated because <b><i>DHCR24</i></b> Needs REST for Robust Expression but <b><i>REST</i></b> Is Poorly Expressed

Cholesterol synthesis in the fetal brain is inhibited because activity of DHCR24 (24-dehydrocholesterol reductase) is insufficient, causing concentrations of the precursor desmosterol to increase temporarily to 15-25% of total sterols at birth. We demonstrate that failure of <i>DHCR24</i> to be adequately upregulated during periods of elevated cholesterol synthesis in the brain results from the presence in its promoter of the repressor element 1 (RE1) nucleotide sequence that binds the RE1-silencing transcription factor (REST) and that REST, generally reduced in neural tissues, uncharacteristically but not without precedent, enhances <i>DHCR24</i> transcription. <i>DHCR24</i> and <i>REST</i> mRNA levels are reduced 3- to 4-fold in fetal mouse brain compared to liver (p < 0.001). Chromatin immunoprecipitation assays suggested that REST binds to the human <i>DHCR24</i> promoter in the vicinity of the predicted human RE1 sequence. Luminescent emission from a human <i>DHCR24</i> promoter construct with a mutated RE1 sequence was reduced 2-fold compared to output from a reporter with wild-type RE1 (p < 0.005). Silencing <i>REST</i> in HeLa cells resulted in significant reductions of <i>DHCR24</i> mRNA (2-fold) and DHCR24 protein (4-fold). As expected, relative concentrations of Δ²⁴-cholesterol precursor sterols increased 3- to 4-fold, reflecting the inhibition of DHCR24 enzyme activity. In contrast, mRNA levels of <i>DHCR7</i> (sterol 7-dehydrocholesterol reductase), a gene essential for cholesterol synthesis lacking an RE1 sequence, and concentrations of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase) enzyme protein were both unaffected. Surprisingly, a dominant negative fragment of REST consisting of just the DNA binding domain (about 20% of the protein) and full-length REST enhanced <i>DHCR24</i> expression equally well. Furthermore, RE1 and the sterol response element (SRE), the respective binding sites for REST and the SRE binding protein (SREBP), are contiguous. These observations led us to hypothesize that REST acts because it is bound in close proximity to SREBP, thus amplifying its ability to upregulate <i>DHCR24</i>. It is likely that modulation of <i>DHCR24</i> expression by REST persisted in the mammalian genome either because it does no harm or because suppressing metabolically active DHCR24 while providing abundant quantities of the multifunctional sterol desmosterol during neural development proved useful

Ethnic differences in effects of maternal pre-pregnancy and pregnancy adiposity on offspring size and adiposity

CONTEXT: Maternal adiposity and overnutrition, both before and during pregnancy, plays a key role in the subsequent development of obesity and metabolic outcomes in offspring.OBJECTIVE:We explored the hypothesis that maternal adiposity (pre-pregnancy and at 26-28 weeks' gestation) and mid-pregnancy gestational weight gain (GWG) are independently associated with offspring size and adiposity in early childhood, and determined whether these effects are ethnicity dependent.DESIGN:In a prospective mother-offspring cohort study (N = 976, 56% Chinese, 26% Malay, and 18% Indian), we assessed the associations of offspring size (weight, length) and adiposity (subscapular and triceps skinfolds), measured at birth and age 6, 12, 18, and 24 mo, with maternal pre-pregnancy body mass index (ppBMI), mid-pregnancy GWG, and mid-pregnancy four-site skinfold thicknesses (triceps, biceps, subscapular, suprailiac).RESULTS: ppBMI and mid-pregnancy GWG were independently associated with postnatal weight up to 2 y and skinfold thickness at birth. Weight and subscapular and triceps skinfolds at birth increased by 2.56% (95% confidence interval, 1.68-3.45%), 3.85% (2.16-5.57%), and 2.14% (0.54-3.75%), respectively for every SD increase in ppBMI. Similarly, a one-SD increase in GWG increased weight and subscapular and triceps skinfolds at birth by 2.44% (1.66-3.23%), 3.28% (1.75-4.84%), and 3.23% (1.65-4.84%), respectively. ppBMI and mid-pregnancy suprailiac skinfold independently predicted postnatal skinfold adiposity up to 2 years of age, whereas only GWG predicted postnatal length. The associations of GWG with postnatal weight and length were present only among Chinese and Indians, but not Malays (P &lt; .05 for interaction).CONCLUSIONS: ppBMI and GWG are independent modifiable factors for child size and adiposity up to 2 years of age. The associations are ethnic-dependent, and underscore the importance of ethnic specific studies before generalizing the applicability of risk factors reported in other population