The objective of this study is to investigate the expression of autophagy-related proteins (LC3 and beclin-1) in human placentas and the changes they undergo in the placentas from pregnancies complicated by preeclampsia (PE) and to explore the regulatory mechanisms of these proteins in JEG-3 cells in response to hypoxia or cytokine treatment.The presence of autophagosomes was confirmed with electron microscopy and the expression of LC3 and beclin-1 by immunoimaging methods in human placental trophoblasts. Compared with the placentas from normal pregnancies, the expression of LC3-II protein, but not beclin-1, was increased in the placentas from severe PE. In JEG-3 cells, hypoxia (O(2) < 1%) induced a modest but not significant increase in the expression of LC3-II with a significant decrease in the expression of beclin-1. Meanwhile, TNF-alpha treatment induced a significant increase in the expression of LC3-II without a significant change in the expression of beclin-1. Our data suggests that increased autophagic activity in the placenta may be implicated in the pathophysiology of PE.
The temperature dependence of the Mott metal-insulator transition (MIT) is studied with a VO2-based two-terminal device. When a constant voltage is applied to the device, an abrupt current jump is observed with temperature. With increasing applied voltages, the transition temperature of the MIT current jump decreases. We find a monoclinic and electronically correlated metal (MCM) phase between the abrupt current jump and the structural phase transition (SPT). After the transition from insulator to metal, a linear increase in current (or conductivity) is shown with temperature until the current becomes a constant maximum value above TSP T ≈68• C. The SPT is confirmed by micro-Raman spectroscopy measurements. Optical microscopy analysis reveals the absence of the local current path in micro scale in the VO2 device. The current uniformly flows throughout the surface of the VO2 film when the MIT occurs. This device can be used as a programmable critical temperature sensor.PACS numbers: 71.27. +a, 71.30.+hThe first-order Mott discontinuous metal-insulator transition (MIT) has been studied as a function of temperature in numerous materials such as Ti 2 O 3 , V 2 O 3 , and VO 2 etc [1]. Almost all have a transition temperature, T MIT , below room temperature except VO 2 which has T MIT ≈68• C. In particular, VO 2 thin films were used for fabrication of two-and three-terminal devices controlled by an electric field [2]. A high-speed Mott switching device using an abrupt current jump as observed in I-V measurements was predicted for manufacturing in the nano-level transistor regime [3,4].Moreover, Raman experiments [5] for a VO 2 film have showed monoclinic-insulator peaks after the film had undergone an electric-field-induced transition from an insulator to a metal. Furthermore, tetragonal-metal peaks have been associated with the structural phase transition (SPT) above 68• C. Also no evidence of phonon softening near the transition temperature has been found by the temperature dependence of Raman spectra measured with a VO 2 single crystal and a thin film [6]. These results support the electron correlation model of the MIT. However, some reports argue that the electric field-induced MIT is due to Joule heating by current and is accompanied by SPT, and that, furthermore, the local current path or current filament formed by the dielectric breakdown [7] can also cause the jump (MIT). The dielectric breakdown was described by depinning and the collective transport of charge carriers above a threshold voltage. Here, we try to elucidate this ambiguity through the analysis of our present research.Another interesting aspect in VO 2 is that the T MIT can be modified by doping [8,9] and stress [10]. VO 2 thin films deposited on (001) and (110) TiO 2 substrates showed a modified T MIT of 27 and 96• C, respectively, where the c-axis length was stressed by a lattice mismatch between the film and the substrate [10]. The modification of the T MIT by doping and stress is restricted to within a fixed temperature, whereas the T MIT indu...
Background Hydroxychloroquine (HCQ) is regarded as a mainstay in the treatment of systemic lupus erythematosus (SLE) because of its efficacy in preventing flares, achieving remission, and reducing overall mortality. However, the impact of HCQ on pregnancy outcomes remains controversial. Objective We aimed to investigate the effect of HCQ on pregnancy outcomes in patients with SLE. Methods We performed a retrospective cohort study of 151 pregnancies in 122 patients with SLE (80 pregnancies in the HCQ treatment group and 71 pregnancies in the HCQ nontreatment group). We reviewed baseline characteristics including maternal comorbidities such as antiphospholipid syndrome, lupus nephritis, and autoimmune hepatitis. Pregnancy outcomes (preeclampsia, preterm delivery, and fetal growth restriction) and neonatal outcomes (gestational age at delivery and birth weight) were compared between HCQ treatment and nontreatment groups. Results Preeclampsia was significantly less complicated (7.5% vs 19.7%, p = 0.032) and neonatal birth weight was significantly greater (2757.0 ± 583.5 g vs 2542.3 ± 908.3 g, p = 0.001) in the HCQ treatment group than in the HCQ nontreatment group. Multiple logistic analysis adjusting for body mass index (BMI), lupus nephritis, serum uric acid, and estimated glomerular filtration rate revealed HCQ treatment was associated with exceedingly lower risk of preeclampsia in SLE pregnancy (odds ratio (OR) 0.106 (confidence interval (CI) 0.017–0.671)). Other independent risk factors for preeclampsia were a high prepregnancy BMI (OR 1.575 (CI 1.114–2.227)) and low eGFR level (OR 0.931 (CI 0.886–0.979)) before pregnancy. Conclusion Our data showed pregnancy outcomes in SLE patients can be improved in the HCQ treatment group with about 90% reduction of preeclampsia.
We investigated the vitamin D status of Korean women during pregnancy and assessed the effects of vitamin D deficiency on two pregnancy outcomes; preterm births and the births of small for gestational age. We measured the serum 25-hydroxyvitamin D levels in 220 pregnant Korean women who were recruited prospectively and compared these levels with those of 500 healthy non-pregnant women. We analyzed vitamin D status according to patient demographics, season, and obstetrical characteristics; moreover, we also assessed pregnancy outcomes. The overall prevalence of vitamin D deficiency(<20 ng/mL) in pregnant women and healthy non-pregnant women was 77.3% and 79.2%; respectively; and the prevalence of severe vitamin D deficiency (<10 ng/mL) was 28.6% and 7.2%; respectively (p < 0.05). Vitamin D deficiency was more prevalent in the winter (100%) than in the summer (45.5%) in pregnant Korean women. A higher risk of vitamin D deficiency was observed in the first trimester than in the third trimester (adjusted OR 4.3; p < 0.05). No significant association was observed between vitamin D deficiency and any of the pregnancy outcomes examined. Further research focusing on the long-term consequences of vitamin D deficiency during pregnancy in Korean women is warranted.
Pattern-dependent effects are a key concern in chemical-mechanical polishing (CMP) processes. In oxide CMP, variation in the interlevel dielectric (ILD) thickness across each die and across the wafer can impact circuit performance and reduce yield. In this work, we present new test mask designs and associated measurement and analysis methods to efficiently characterize and model polishing behavior as a function of layout pattern factors-specifically area, pattern density, pitch, and perimeter/area effects. An important goal of this approach is rapid learning which requires rapid data collection. While the masks are applicable to a variety of CMP applications including back-end, shallow-trench, or damascene processes, in this study we focus on a typical interconnect oxide planarization process, and compare the pattern-dependent variation models for two different polishing pads. For the process and pads considered, we find that pattern density is a strongly dominant factor, while structure area, pitch, and perimeter/area (aspect ratio) play only a minor role.
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