25 research outputs found

    Compressive deformation of polycrystalline Ni-Mn-Ga alloys near chemical ordering transition temperature

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    Ferromagnetic shape memory Ni-Mn-Ga alloys exhibit an ordered L21 to partially ordered B2 transition at temperatures 873–1073 K. Based on the isothermal compressive results, it is demonstrated that L21 phase was brittle near ordering temperature, but the B2 phase was excellent above the chemical ordering temperature. In the compressive mode at temperatures of 473–1273 K and strain rates of 0.001–1 s−1, the plastic deformation mechanism was found to be strongly dependent on the Zener-Hollomon parameter Z: the dynamic recrystallization was the dominant mechanism at the low Z region in the B2 state, then with increasing Z the dynamic recovery and ordering transition from B2 to L21 occurred, finally only dynamic recovery existed at the high Z region in the L21 state. Based on the processing map constructed from the isothermal compressive curves, hot extrusion of Ni-Mn-Ga alloy with ratio as high as 9:1 was achieved at 1273 K. This proved that polycrystalline Ni-Mn-Ga alloys are strikingly facile for large plastic deformation in the B2 state by dynamic recrystallization at temperatures around 1273 K and strain rate 0.03 s−1, which affords a viable temperature and strain rate processing window for this intrinsically brittle alloy.</p

    Relationship between PNPLA3 rs738409 polymorphism and decreased kidney function in children with NAFLD

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    Emerging evidence suggests that patatin‐like phospholipase domain‐containing protein‐3 (PNPLA3) rs738409 genotype (the major genetic variant associated with susceptibility to non‐alcoholic fatty liver disease [NAFLD]) is associated with decreased kidney function in adults. Currently, it is uncertain whether this association also occurs in children/adolescents and whether any association is independent of liver disease severity. We enrolled a sample of 142 consecutive Caucasian children and adolescents with biopsy‐proven NAFLD, presenting to the Liver Unit of the “Bambino GesĂč” Children's Hospital. Glomerular filtration rate (e‐GFR) was estimated using the Bedside Schwartz equation, whereas 24‐hour proteinuria was measured with a radioimmunoassay method. Genotyping for PNPLA3 rs738409 genotype was undertaken using the TaqMan SNP genotyping allelic discrimination method. Overall, forty‐five children had G/G, 56 had G/C and 41 had C/C PNPLA3 rs738409 genotype, respectively. Children with G/G genotype had significantly lower e‐GFR (107.5±20 vs. 112.8±18 vs. 125.3±23 mL/min/1.73 m2, p=0.002) and higher 24‐hour proteinuria (58.5±21 vs. 53.9±22 vs. 42.9±20 mg/day, p=0.012) compared to those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, HOMA‐estimated insulin resistance and biopsy‐confirmed non‐alcoholic steatohepatitis (NASH) and stage of liver fibrosis, the presence of rs738409 G/G genotype was independently associated with both lower e‐GFR (ÎČ coefficient: ‐23.6, 95% CI ‐36.3 to ‐10.8, p&lt;0.001) and higher 24‐hour proteinuria (ÎČ coefficient: 15.3, 95% CI 1.12 to 30.5, p=0.046)

    Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis

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    Cholesterol synthesis is among the oldest metabolic pathways, consisting of the Bloch and Kandutch-Russell branches. Following lanosterol, sterols of both branches are proposed to be dedicated to cholesterol. We challenge this dogma by mathematical modeling and with experimental evidence. It was not possible to explain the sterol profile of testis in cAMP responsive element modulator tau (Crem τ) knockout mice with mathematical models based on textbook pathways of cholesterol synthesis. Our model differs in the inclusion of virtual sterol metabolizing enzymes branching from the pathway. We tested the hypothesis that enzymes from the cytochrome P450 (CYP) superfamily can participate in the catalysis of non-classical reactions. We show that CYP enzymes can metabolize multiple sterols in vitro, establishing novel branching points of cholesterol synthesis. In conclusion, sterols of cholesterol synthesis can be oxidized further to metabolites not dedicated to production of cholesterol. Additionally, CYP7A1, CYP11A1, CYP27A1, and CYP46A1 are parts of a broader cholesterol synthesis network.Slovene Research Agency [P1-0104]; US National Institutes of Health [R37 CA090426]; Slovene Human Resources Development and Scholarship FundOpen Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
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