Search

The mechanic performance of ejecting pneumatic fire extinguisher is determined by the following parameters: air speed at funnel exit, outfire range and ejecting stability; and the second and third parameters depend on the fire extinguishing agent pellet's velocity on funnel exit and the amount of fire extinguishing agent pellets detained in the funnel when extinguisher is working. In this research, the CFD-DEM coupling model was adopted to simulate the working process of ejecting pneumatic fire extinguisher, and the type of 6MF-30 pneumatic extinguisher was used to test the reliability of the coupling model. The funnel throat angle X1, the adding position of fire extinguishing agent X2, and the funnel length X3 were selected as the influencing factors, and total 23 experiments were conducted by the simulation model under the quadratic orthogonal rotation design. The virtual tunnel was designed according to the tunnel equipped to 6MF-30 pneumatic extinguisher. The virtual fire extinguishing agent pellets were found on the EDEM interface, coupled to the original CFD by Lagrangian model. The pretest results showed that this model had strong convergence which was proved by its stable airflow performance when running at the time of 0.2-0.25 s, and stable pellet number when running at 0.34 s. The air velocity at exit calculated by the CFD-DEM coupling model was similar to the theoretical value. It could be found that the number of aggregating virtual pellets detained in the region between the air tunnel and the fire extinguishing agent's channel was consistent with the result of research by other scholars. The simulating experiment data were exported for analyzing. The average velocity in axial direction on each point at funnel exit was read by Fluent, and after subtracting the average value 197.550, the deviation data of the 23 experiments were got and selected as the outlet wind velocity (index 71). The max virtual pellet velocities in axial direction monitored by EDEM within 0-0.4 s of all experiments were selected as the spouting velocity (index Y2). The vertical coordinates of every virtual pellet at 0.37, 0.38, 0.39, 0.4 s in all experiments were read by EDEM, and 'countif' function was used to calculate the number of virtual pellet located in the tunnel (as assessment index Y3) when working. After the significant test and the variance analysis, the regression equation building was done by using SAS9.1. The result showed that the fire extinguishing agent pellet's velocity on funnel exit and the amount of fire extinguishing agent pellets detained in the funnel were significantly correlated to the three factors (P<0.0001, P<0.001 respectively), but the air speed at funnel exit had no correlation with these factors. By using response surface method combined with weighting method, the optimal aggregative index could be obtained under the condition that the funnel throat angle was 20°, the adding position of fire extinguishing agent was 140 mm and the funnel length was 700 mm. Under this condition, the efficiency of ejecting pneumatic fire extinguisher was mostly improved. The virtual test designed by the optimized parameters showed that the fire extinguishing agent pellet's velocity on funnel exit increased to 41.24 m/s, and the number of fire extinguishing agent pellets detained in the funnel decreased to 209. The verify test of the physical prototype indicated that the optimized parameters could improve the working effect of ejecting pneumatic fire extinguisher, which was manifested in extending the outfire range by 2.15 m, reducing the possibility of reburning and shortening the outfire time by 1.7 s. [ABSTRACT FROM AUTHOR]

ABSTRACT The p. Arg116 His mutation in the heat shock transcription factor-4 ( HSF4) has been associated with age-related cataracts, but it is also seen in 2% of the normal population, indicating either reduced penetrance or that the normal subjects were not old enough to express the phenotype. Based on the proximity of p. Arg116 His to two known mutations in the DNA-binding domain of HSF4, namely, p. Leu114 Pro and p. Arg119 Cys, which segregate with childhood lamellar cataract, we tested the possibility that this phenotype may have been missed by the ophthalmologist and/or that it did not spread to the visual axis so as to affect vision significantly. Here, we demonstrate via BAC (bacterial artificial chromosome) transgenesis that p. Arg116 His recreates the childhood lamellar cataract in mice suggesting that incomplete penetrance associated with early cataracts may not be an absence but a limitation of the detection of the phenotype. [ABSTRACT FROM AUTHOR]

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11 hydroxysteroid dehydrogenase type 1 (11β-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11β-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11β- HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancerpromoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11β-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser660 HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome [ABSTRACT FROM AUTHOR]

A portable pneumatic extinguisher is an effective device that has been widely used for forest and grassland fire extinguishing in China. In order to enhance the effective range and rate of discharge of portable pneumatic extinguishers, a new method to weaken air velocity attenuation by increasing the flow rate using an air ejector was proposed and investigated in this study. This research belongs to the category of subsonic air ejector. First, the turbulivity of air jet "c" has been updated to the value of 0.106 by experiments. It is necessary to use this factor for the calculation of air velocity where 2.5 m downstream from the centrifugal fan which defined as u2.5. Experimental and the CFD (Computational Fluid Dynamics) methods are applied to investigate the influence on the performance of the air ejector. Three parameters were characterized: converging angle of entraining chamber θ; diameter of the mixing chamber Dm and the nozzle position (NXP) S. Up to 240 different models were established and meshed by Gambit 2.3, and then simulated and calculated by Fluent 6.3 with the turbulence model of RNG k-epsilon. Consequently, 240 different results containing the flow rate of nozzle outlet cross-section mp, the entrainment flow rate me, the flow rate of the mixing chamber outlet cross-section mc, and the air velocity of a mixing chamber outlet cross-section uc were acquired. Based on this data, the response surfaces for u2.5 and entrainment ratio that are used to investigate the interaction between Dm, θ and S to u2.5 and entrainment ratio were established. The results indicated that the parameters Dm and θ have a great influence on u2.5 and entrainment ratio. It was also demonstrated that the interaction between Dm and θ is significant. However, parameter S gave a relatively delicate influence on u2.5 and entrainment ratio, and also the interaction with the other parameters was weak. In addition, to find out the mechanism of interaction between Dm and θ, three groups of different pressure fields have been investigated and compared as well. It indicates that a high value of θ (when θ < 36.25°) could create a relatively significant negative pressure zone in the mixing chamber, which requires a larger Dm to provide sufficient air input, and as a consequence u2.5 and entrainment ratio increase accordingly. Because of the negative pressure zone nearby the nozzle outlet, the effective power of the centrifugal fan and engine are both increased. The optimum value of θ is 36.25°, and when Dm equals to 144 mm, u2.5 could reach the maximum value. The maximum u2.5, which was gained by experiments using an ejecting pneumatic extinguisher, was 36.4 m/s. Meanwhile, the value of u2.5 could keep adding up as Dm continued to increase, but the range of Dm has been limited by the design and practical applicability of the portable pneumatic extinguisher. [ABSTRACT FROM AUTHOR]

Purpose: Ocular Albinism type 1 (OA1) is a disease caused by mutations in the OA1 gene and characterized by the presence of macromelanosomes in the retinal pigment epithelium (RPE) as well as abnormal crossing of the optic axons at the optic chiasm. We showed in our previous studies in mice that Oa1 activates specifically Gαi3 in its signaling pathway and thus, hypothesized that a constitutively active Gαi3 in the RPE of Oa1−/− mice might keep on the Oa1 signaling cascade and prevent the formation of macromelanosomes. To test this hypothesis, we have generated transgenic mice that carry the constitutively active Gαi3 (Q204L) protein in the RPE of Oa1−/− mice and are now reporting the effects that the transgene produced on the Oa1−/− RPE phenotype. Methods: Transgenic mice carrying RPE-specific expression of the constitutively active Gαi3 (Q204L) were generated by injecting fertilized eggs of Oa1−/− females with a lentivirus containing the Gαi3 (Q204L) cDNA. PCR, Southern blots, Western blots and confocal microscopy were used to confirm the presence of the transgene in the RPE of positive transgenic mice. Morphometrical analyses were performed using electron microscopy to compare the size and number of melanosomes per RPE area in putative Oa1−/−, Gαi3 (Q204L) transgenic mice with those of wild-type NCrl and Oa1−/− mice. Results: We found a correlation between the presence of the constitutively active Gαi3 (Q204L) transgene and the rescue of the normal phenotype of RPE melanosomes in Oa1−/−, Gαi3 (Q204L) mice. These mice have higher density of melanosomes per RPE area and a larger number of small melanosomes than Oa1−/− mice, and their RPE phenotype is similar to that of wild-type mice. Conclusions: Our results show that a constitutively active Gαi3 protein can by-pass the lack of Oa1 protein in Oa1−/− mice and consequently rescue the RPE melanosomal phenotype. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the role of G[sub i2] alpha protein in the regulation of cardiac calcium channels. Methodology; Results of the study; Discussion.

Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincided with decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.

Long-term glucocorticoid exposure increases the risk for developing type 2 diabetes. Prereceptor activation of glucocorticoid availability in target tissue by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic syndrome. We explored whether the tissue-specific modulation of 11β-HSD1 and H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and lipolysis and analyzed the effects of 11β-HSD1 inhibition on the key lipid metabolism genes and insulin-signaling cascade. We observed that corticosterone (CORT) treatment increased expression of 11β-HSD1 and H6PDH and induced lipase HSL and ATGL with suppression of p-Thr(172) AMPK in adipose tissue of C57BL/6J mice. In contrast, CORT induced adipose insulin resistance, as reflected by a marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr(308) Akt/PKB. Furthermore, 11β-HSD1 shRNA attenuated CORT-induced 11β-HSD1 and lipase expression and improved insulin sensitivity with a concomitant stimulation of pThr(308) Akt/PKB and p-Thr(172) AMPK within adipose tissue. Addition of CORT to 3T3-L1 adipocytes enhanced 11β-HSD1 and H6PDH and impaired p-Thr(308) Akt/PKB, leading to lipolysis. Knockdown of 11β-HSD1 by shRNA attenuated CORT-induced lipolysis and reversed CORT-mediated inhibition of pThr(172) AMPK, which was accompanied by a parallel improvement of insulin signaling response in these cells. These findings suggest that elevated adipose 11β-HSD1 expression may contribute to glucocorticoid-induced insulin resistance and adipolysis., (Copyright © 2015 the American Physiological Society.)