We have previously reported that the exposure of human HepG2 cells to hypoxic conditions results in the overexpression of human insulin-like growth factor II (IGF-II) mRNA whose size is 6.0 kb. This ...particular size of IGF-II mRNA is transcribed under the control of the IGF-II P3 promoter. In the present study, to delineate the molecular mechanism for the activation of the IGF-II gene, we examined the induction of P3 promoter activity in HepG2 cells by hypoxia in the transient expression system. In this system, hypoxia induced a linear increase within 24 h in the expression of luciferase that was driven by the IGF-II P3 promoter. To further delineate which factors mediate this response, the expression pattern of regulators of the P3 promoter, Egr-1, Sp1, and WT1, were analyzed by reverse transcription-PCR and Northern blot analysis. We found that hypoxia increased the expression of Egr-1 but not of Sp1. In contrast, the level of WT1, a repressor of IGF-II expression, was markedly decreased during hypoxia. The mRNA stability assay revealed that the induction of transcription is the mechanism of underlying Egr-1 mRNA elevation. We then investigated the effects of hypoxia on the DNA binding activity of Egr-1. Both electrophoretic mobility shift assay and supershift assay demonstrated that the DNA binding activity of the Egr-1 protein was increased by hypoxia. In addition, the level of Egr-1 protein was also increased under the hypoxia as determined by Western blot analysis. Cotransfection of HepG2 cells with an Egr-1 expression vector and an IGF-II P3 promoter-luciferase reporter plasmid showed that the transcription of IGF-II was activated by Egr-1 in a dose-dependent manner. Moreover, the elevation of IGF-II P3 promoter activity was induced synergistically by the cotreatment of hypoxia with Egr-1 overexpression. Deletion of sequences in the IGF-II P3 promoter containing Egr-1 binding sites did not respond to hypoxic stress. Taken together, these data strongly indicate that hypoxia-induced IGF-II expression in HepG2 cells is due to the enhanced activity of Egr-1 on the IGF-II P3 promoter and that the Egr-1 binding site in the IGF-II P3 promoter is essential for the transcriptional regulation of IGF-II under hypoxic conditions.
An amorphous Si film with thickness of 350
nm was fabricated on both Cu substrate and Ni film (under layer)/Cu substrate by direct current (DC) and radio frequency (RF) magnetron sputtering. The ...surface morphology, crystallographic structure and electrochemical properties were investigated. Flat surface was formed in Si/Cu film, whereas in Si/Ni/Cu film a rough surface was formed consisting of Si clusters. In a Si/Li half-cell test with current densities of 210 (0.05
C-rate), 810 (0.2
C-rate) and 4200
mA
g
−1 (1
C-rate), the surface-modified Si film electrode exhibited a significantly improved cycle performance compared to the Si film deposited on only Cu substrate. LiFePO
4/Si full cell tested at current density 85
mA
g
−1 of (0.5
C-rate) displayed the first charge capacity of 154.0
mAh
g
−1, corresponding to 90.5% of theoretical capacity of LiFePO
4 and the capacity retention of 79.4% at 20th cycle.
There is no clear consensus on the recommended second-line treatment for patients with metastatic pancreatic cancer who have disease progression following gemcitabine-based therapy. We ...retrospectively evaluated the clinical outcomes of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (FL) and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) in patients who had failed on the first-line gemcitabine-based therapy.
From January 2015 to August 2019, 378 patients with MPC who had received nal-IRI/FL (n = 104) or FOLFIRINOX (n = 274) as second-line treatment across 11 institutions were included in this retrospective study.
There were no significant differences in baseline characteristics between groups, except age and first-line regimens. With a median follow-up of 6 months, the median progression-free survival (PFS) was 3.7 months with nal-IRI/FL versus 4.6 months with FOLFIRINOX (P = 0.44). Median overall survival (OS) was 7.7 months with nal-IRI/FL versus 9.7 months with FOLFRINOX (P = 0.13). There was no significant difference in PFS and OS between the two regimens in the univariate and multivariate analyses. The subgroup analysis revealed that younger age (<70 years) was associated with better OS with FOLFIRINOX. In contrast, older age (≥70 years) was associated with better survival outcomes with nal-IRI/FL. Adverse events were manageable with both regimens; however, the incidence of grade 3 or higher neutropenia and peripheral neuropathy was higher in patients treated with FOLFIRINOX than with nal-IRI/FL.
Second-line nal-IRI/FL and FOLFIRINOX showed similar effectiveness outcomes after progression following first-line gemcitabine-based therapy. Age could be the determining factor for choosing the appropriate second-line therapy.
•This multicenter retrospective study investigated nal-IRI/FL and FOLFIRINOX outcomes after gemcitabine-based therapy.•We found no significant differences in outcome between nal-IRI/FL and FOLFIRINOX treatment.•Both regimens were well tolerated; however, neutropenia and peripheral neuropathy were more frequent with FOLFIRINOX.•Age (cut-off, 70 years) showed differential efficacy between chemotherapy regimens.
Copper incorporated zinc oxide (CuZnO) thin films were synthesized onto the glass and tin doped indium oxide (ITO) coated glass substrates at 450°C by simple and cost-effective spray pyrolysis ...technique (SPT). The X-ray diffraction (XRD) patterns confirmed the polycrystalline nature of the films having hexagonal crystal structure. A compact and granular morphology was observed for all deposited films. The absorption edge of the CuZnO films showed a red shift, meaning that the optical band gap energy decreases as copper doping concentration increases. The room-temperature photoluminescence (PL) spectra of CuZnO films revealed the ultraviolet (UV) near band edge emission peak at ~373nm and the defect related level emission at ~447nm. Furthermore, films deposited onto conducting ITO coated glass substrates were tested for their photoelectrochemical (PEC) performance in 0.5M Na2SO4 electrolyte solution. The fill factor (FF) and open circuit voltage (Voc) values were improved for CuZnO films.
Booster pump system (BPS) can control the number of revolutions through an inverter by combining two or more vertical or horizontal centrifugal pumps in a series. Efficiency and energy savings, the ...most appealing aspects of booster pump systems, can be improved by controlling the operating conditions of individual pumps by measuring the flow rate of each pump. For improved operation, a booster pump system with a flow sensor to detect individual pump flow rates and a control algorithm to manage each low and high flow rate pump’s revolutions per minute are critical. To achieve this, first, the turbine-type flow sensor was developed through computational fluid dynamics and experimentation. The flow sensor was improved using computational fluid dynamics, and its accuracy was validated through experiments. The resulting flow measurement accuracy of the designed flow sensor was within 4%, with a measurement uncertainty of 0.4%. In addition, an experimental pump facility was built and used to evaluate booster pump system performance to investigate the energy saving rate. Then, after driving one low-flow rate pump at a set pressure, the flow and frequency control operation algorithm was used. This algorithm increased the allowed output of the drive pump by increasing the inverter’s frequency. When the frequency corresponding to the allowed output is achieved in the low-flow rate pump rather than the high flow rate pump, power savings increased due to the low-flow rate pump’s extended drive range. The investigations on the developed system’s energy consumption revealed that the energy savings were approximately 6.2% compared to the conventional system, depending on the system in question. The development of a booster pump system with a flow sensor was tested, and it was found to be effective.
The effect of Off-state stress on a propagation delay (tPD) and a data-valid window (tDV) was characterized. The experimental result showed that the Vth of PMOSET reduced due to the electron trapping ...into the nitride in the STI, thus resulting in the decrease in tDV. The extracted time slope n of NBTI, off-state degradation, \Delta \text{tPD}, \Delta \text{tDV} were ∼0.23, ∼0.4, ∼0.32, and ∼0.4 respectively. It indicates that the degradation of tDV was dominated by the off-state stress. Thus, the mechanism of off-state degradation was investigated by varying the physical dimensions of the transistor and STI structure. Moreover, an empirical model of tDV degradation was proposed using device models such as off-state stress, NBTI, HCI, and it matched well with an experimental result measured at the system level. With this model, various processes such as implantation, SiGe channel, and STI structure were optimized, and as a result, the off-state stress is well controlled.
Comorbid conditions are important in the survival of kidney transplant recipients. The weights assigned to comorbidities to predict survival may vary based on the type of index disease and advances ...in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in renal allograft recipients (mCCI-KT), thereby improving risk stratification for mortality.
A total of 3765 recipients in a multicenter cohort were included to develop a comorbidity score. The weights of the comorbidities, per the CCI, were recalibrated using a Cox proportional hazards model.
Peripheral vascular disease, liver disease, myocardial infarction, and diabetes in the CCI were selected from the Cox proportional hazards model. Thus, the mCCI-KT included 4 comorbidities with recalibrated severity weights. Whereas the CCI did not discriminate for survival, the mCCI-KT provided significant discrimination for survival using the Kaplan-Meier method and Cox regression analysis. The mCCI-KT showed modest increases in c-statistics (0.54 vs 0.52, P = .001) and improved net mortality risk reclassification by 16.3% (95% confidence interval, 3.2–29.4; P = .015) relative to the CCI.
The mCCI-KT stratifies the risk for mortality in renal allograft recipients better than the CCI, suggesting that it may be a preferred index for use in clinical practice.
The aim of this study was to evaluate the risk factors for dislocation of the bearing after a mobile-bearing Oxford medial unicompartmental knee replacement (UKR) and to test the hypothesis that ...surgical factors, as measured from post-operative radiographs, are associated with its dislocation From a total of 480 UKRs performed between 2001 and 2012, in 391 patients with a mean age of 66.5 years (45 to 82) (316 female, 75 male), we identified 17 UKRs where bearing dislocation occurred. The post-operative radiological measurements of the 17 UKRs and 51 matched controls were analysed using conditional logistic regression analysis. The post-operative radiological measurements included post-operative change in limb alignment, the position of the femoral and tibial components, the resection depth of the proximal tibia, and the femoral component-posterior condyle classification. We concluded that a post-operative decrease in the posterior tibial slope relative to the pre-operative value was the only significant determinant of dislocation of the bearing after medial Oxford UKR (odds ratio 1.881; 95% confidence interval 1.272 to 2.779). A post-operative posterior tibial slope < 8.45° and a difference between the pre-operative and post-operative posterior tibial slope of > 2.19° may increase the risk of dislocation.
An increasing demand for esthetic restorations has resulted in the development of new ceramic systems, but the fracture of veneering ceramics still remains the primary cause of failure. Porcelain ...repair frequently involves replacement with composite resin, but the bond strength between composite resin and all-ceramic coping materials has not been studied extensively.
The purpose of this study was to evaluate the tensile bond strength of composite resin to 3 different all-ceramic coping materials with various surface treatments.
Thirty specimens (10 × 10 × 2 mm) each of lithium-disilicate ceramic (IPS Empress2 E), alumina ceramic (In-Ceram Alumina I), and zirconia ceramic (Zi-Ceram Z) were fabricated. Feldspathic ceramic (Duceram Plus F) was used as the control. Each material was divided into 3 groups (n=10), and 3 different surface treatments were performed: airborne-particle abrasion with 50-μm alumina particles (Ab); airborne-particle abrasion with 50-μm alumina particles and acid etching with 4% hydrofluoric acid (Ae); or airborne-particle abrasion with 30-μm alumina particles modified with silica acid (Si). After surface treatment of ceramic specimens, composite resin cylinders (5-mm diameter × 10-mm height) were light polymerized onto the ceramic specimens. Each specimen was subjected to a tensile load at a crosshead speed of 2 mm/min until fracture. The fracture sites were examined with scanning electron microscopy to determine the location of failure during debonding and to examine the surface treatment effects. Two-way analysis of variance and the Duncan multiple comparison test (α=.05) were used to analyze the bond strength values.
There were significant differences in the bond strengths for both ceramics (
P<.001) and surface treatments (
P<.001) and the interaction (
P<.001). The Duncan analysis yielded the following statistical subsets of the bond strength values: (FAe, ISi, EAe, ZSi) > FAb > (FSi, EAb, ESi) (IAb, IAe) > (ZAe, ZAb). The results illustrate no differences within the parentheses but statistically significant differences among the groups.
Alumina and zirconia ceramic specimens treated with a silica coating technique, and lithium disilicate ceramic specimens treated with airborne-particle abrasion and acid etching yielded the highest tensile bond strength values to a composite resin for the materials tested.
This study compared the shoulder muscular performance and lean mass between elite and recreational swimmers.Thirty elite swimmers (mean age ± standard deviation = 23.1 ± 3.5 years) and 21 ...recreational swimmers (mean age ± standard deviation = 20.8 ± 2.1 years) participated in the study. Maximum muscle strength and time to maximum muscle strength of shoulder flexor, extensor, abductor, and adductor muscles were measured using a handheld dynamometer. Lean mass of the arms and body (excluding the head) were measured using dual-energy x-ray absorptiometry (DXA).Results revealed that compared with recreational swimmers, elite swimmers had higher maximum muscle strength of the shoulder flexor, extensor, abductor, and adductor muscles (all P < .001). The time to reach maximum muscle strength of all shoulder muscles showed no significant difference between the 2 groups (P > .05). The lean mass values in the left arm (P = .037), right arm (P < .001), and whole body (P = .014) were higher in elite swimmers than recreational swimmers.Elite swimmers had greater shoulder maximum muscle strength compared with recreational swimmers though the time taken to reach maximum muscle strength was similar between the 2 groups. Elite swimmers also showed a higher lean mass in both arms and their entire body when compared with recreational swimmers. The results may be useful for recreational swimmers who intend to advance to professional level, and for talent identification and early development of elite swimmers.
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